{"paper_id":"3f6da8a1-488c-44ea-a844-2dbad8adbe6c","body_text":"Photodynamic and photothermal bacteria targeting nanosystems for synergistically combating bacteria and biofilms | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Photodynamic and photothermal bacteria targeting nanosystems for synergistically combating bacteria and biofilms Wenxuan Shi, Ao Zheng, Yu Jin, Zhuoyuan Li, Tanjun Deng, Xiao Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4522338/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jan, 2025 Read the published version in Journal of Nanobiotechnology → Version 1 posted 19 You are reading this latest preprint version Abstract The escalating hazards posed by bacterial infections underscore the imperative for pioneering advancements in next-generation antibacterial modalities and treatments. Present therapeutic methodologies are frequently impeded by the constraints of insufficient biofilm infiltration and the absence of precision in pathogen-specific targeting. In this current study, we have used chlorin e6 (Ce6), zeolitic imidazolate framework-8 (ZIF-8), polydopamine (PDA), and UBI peptide to formulate an innovative nanosystem meticulously engineered to confront bacterial infections and effectually dismantle biofilm architectures through the concerted mechanism of photodynamic therapy (PDT)/photothermal therapy (PTT) therapies, including in-depth research, especially for oral bacteria and oral biofilm. Ce6@ZIF-8-PDA/UBI nanosystem, with effective adhesion and bacteria-targeting, affords a nuanced bacterial targeting strategy and augments penetration depth into oral biofilm matrices. The Ce6@ZIF-8-PDA/UBI nanosystem potentiated bacterial binding and aggregation. Upon exposure to near-infrared (NIR) irradiation, Ce6@ZIF-8-PDA/UBI showed excellent antibacterial effect on S. aureus, E. coli, F. nucleatum , and P. gingivalis and exceptional light-driven antibiofilm activity to P. gingivalis biofilm, which was a result of the efficient bacterial localization mediated by PDA/UBI, as well as the PDT/PTT facilitated by Ce6/PDA interactions. Collectively, these versatile nanoplatforms augur a promising and strategic avenue for controlling infection and biofilm, thereby holding significant potential for future integration into clinical paradigms. The original application of the developed nanosystem in oral biofilms also provides a new strategy for effective oral infection treatment. Biofilm Antibacterial Phototherapy ZIF-8 Ce6 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Bacterial infections have been classified by the World Health Organization (WHO) as one of the leading causes of global mortality over the past 15 years [ 1 ]. According to reports from the National Institutes of Health (NIH) in the United States, as many as 80% of bacterial infections are associated with biofilm formation [ 2 ]. Bacterial biofilms are dense bacterial communities encased in self-produced extracellular polymeric substances (EPSs) that can elude the host's adaptive and innate immune system. Biofilms are particularly concerning in chronic wounds, where they are prevalent in approximately 78.2% of cases, posing a significant hindrance to the healing process [ 3 ]. Closed wounds with biofilm infections still show functional problems, such as a compromised extracellular matrix and impaired barriers, leading to recurring wound problems [ 2 ]. Biofilm formation also occurs in surgical procedures involving implants. Bacteria adhere to the implant during surgery, forming biofilms and causing infections. As these biofilms mature, they release bacteria, which spread widely and cause recurrent infections, ultimately leading to implant failure [ 4 , 5 ]. Notably, oral biofilms represent another highly complex challenge that can lead to chronic oral infections, including dental caries, periodontal diseases, peri-implantitis, and even systemic conditions affecting the gastrointestinal tract and cardiovascular system [ 6 ]. Treating these infections traditionally involves antibiotics, but biofilm-encased bacteria are highly resistant and require prolonged and high-dose antibiotic treatment, which can worsen resistance [ 7 ]. Current approaches to oral biofilm treatment involve periodic mechanical disruption and antimicrobial use, but they often require professional intervention and may not fully resolve secondary infections [ 8 ]. Therefore, there is an urgent need to explore innovative therapeutic strategies to control infections and eradicate biofilms. Photodynamic therapy (PDT) has recently gained recognition as an effective, noninvasive antimicrobial treatment [ 9 ]. Using photosensitizers, PDT generates reactive oxygen species (ROS) when exposed to light [ 10 ], offering advantages such as resistance to drug resistance, painlessness, quick treatment, and minimal tissue damage [ 11 – 13 ]. Chlorin e6 (Ce6), derived from natural chlorophyll and an FDA-approved photosensitizer, has advantages such as efficient ROS generation, brief photosensitization, and strong red-light absorption [ 14 ]. However, Ce6 faces challenges due to its limited water solubility and similar charge to bacteria. The development of an advanced antimicrobial PDT system for efficient photosensitizer release, improved penetration, and prolonged retention is crucial. Therefore, nanocarriers have been increasingly applied to assist in the penetration and transmembrane transport of hydrophobic photosensitizers in biofilms [ 15 – 20 ]. Zeolitic imidazolate framework (ZIF) is a promising nanocarrier with porosity, stability, and tunability [ 21 ]. Simultaneously, the pH-sensitive degradation of ZIF-8 aligns perfectly with the acidic microenvironment inside bacterial biofilms, rendering it an ideal choice for controlled-release photosensitizer platforms such as Ce6 [ 22 ]. Due to the limitations of photosensitizers, PDT sometimes requires a series of rational methods and strategies to work together to achieve better antimicrobial results. It has been reported that the combination of PDT and photothermal therapy (PTT) has an excellent therapeutic effect in treating bacterial infection [ 23 ]. PTT uses photothermal conversion materials under the excitation of a specific light source to convert light energy into heat energy, resulting in excessive heat and leading to protein denaturation or cell membrane damage in bacteria and cells to achieve sterilization, which shows great potential in the treatment of drug-resistant bacteria and bacterial biofilms [ 24 ]. Under the synergistic action of PDT and PTT, the bactericidal effects of Ce6 on S. aureus were significantly enhanced [ 25 ]. The dual-mode antibacterial conjugated nanoparticles had a photothermal effect and sensitized the cells to surrounding oxygen [ 24 ]. Polydopamine (PDA) is an efficient organic photosensitizer with high biocompatibility and biodegradability. Due to its exceptional near-infrared (NIR) absorption and photothermal conversion efficiency, PDA might be an ideal candidate for antibacterial PTT. Moreover, PDA molecules with extensive functional groups, such as amine, catechol, and phenolic hydroxyl groups, can easily interact with other molecules, such as peptides, through functional groups via chemical bonds, electrostatic attraction, or π-π interactions. Similarly, PDA can rapidly form a conformal layer by being deposited on nanoparticle surfaces. PDA may also increase the adhesion of nanocarriers to bacteria to some extent [ 26 ]. Therefore, PDA can be used as a PTT coating on the nanocarrier surface and as a binder for further functional modification. One major challenge in combating biofilms is their robust self-defense mechanisms. Achieving effective biofilm penetration is crucial, but this can be challenging for nanoparticles, even though they can enter biofilm pores. To address this issue, we aimed to enhance nanoparticle performance by modifying them to better adhere to and target bacteria, thus improving antimicrobial penetration. We utilized antimicrobial peptides, such as ubiquicidine (UBI), specifically the UBI (29–41) peptide. It is a cationic peptide chain containing six positively charged amino acids and can selectively bind to bacterial cell membranes through electrostatic forces, particularly at infection sites [ 27 ]. We hypothesized that modifying nanocarriers with UBI (29–41) could enhance bacterial targeting and biofilm penetration by promoting electrostatic interactions with bacterial membranes. To achieve this goal, we coated Ce6-loaded ZIF-8 nanoparticles with PDA/UBI to develop advanced antibacterial treatments for clinical use. This study introduced a novel approach for a metal-organic framework (MOF)-based nanosystem, Ce6@ZIF-8-PDA/UBI, to effectively manage and eliminate biofilm-related infections. We synthesized these nanoparticles using PDA chemistry and grafted UBI to provide more anchors for bacteria and deep penetration into biofilms. We investigated the antibacterial properties of Ce6@ZIF-8-PDA/UBI under NIR irradiation, which significantly improved its activity against S. aureus, E. coli, F. nucleatum, and P. gingivalis compared to that of their counterparts. It also exhibited exceptional light-driven antibiofilm activity against P. gingivalis oral biofilms. This was due to efficient bacterial adhesion mediated by PDA/UBI modifications and synergistic PDT/PTT facilitated by Ce6/PDA interactions. Moreover, we assessed the in vivo effects of the nanosystem on infected wound healing and peri-implant infection control. The Ce6@ZIF-8-PDA/UBI nanosystem, with synergistic PTT and PDT, offers a promising approach for treating bacterial infections and biofilms (Scheme 1 ). Materials and methods Synthesis of Ce6@ZIF-8-PDA/UBI Synthesis of Ce6@ZIF-8: 180 mg of 2-methylimidazole (HMIM) and 20 mg of Zn(NO 3 ) 2 ·6H 2 O were dispersed separately in 1 mL of methanol. A solution of 0.5 mL of Ce6 (1.0 mg/mL in dimethyl sulfoxide) and HMIM (180 mg/mL in methanol) was mixed and stirred for 5 minutes. Then, Zn(NO 3 ) 2 ·6H 2 O (20 mg/mL in methanol) was swiftly added. The obtained solution was stirred at room temperature in the dark for 1.5 hours. Upon completion, the collected Ce6@ZIF-8 was centrifuged and washed, followed by resuspension and storage in the dark at 4°C. Control samples of ZIF-8 nanoparticles were synthesized similarly. To quantify unembedded Ce6, the supernatant was collected and analyzed using a microplate reader (Spark 10M, TECAN, Switzerland) to obtain the OD values. The Ce6 loading efficiency (LE) was then calculated as (Total Ce6 amount-unembedded Ce6 amount)/Ce6@ZIF-8 weight×100%. Synthesis of Ce6@ZIF-8-PDA: Initially, a dopamine solution (3.2 mL, 25 mM in methanol) was introduced to a Ce6@ZIF-8 solution in methanol (32 mL). The resulting mixture was refluxed at 60 ℃ for 7 hours. Next, the resulting Ce6@ZIF-8-PDA was subjected to a washing and resuspension process. Synthesis of Ce6@ZIF-8-PDA/UBI: Next, 400 µL of UBI solution (8 mg/mL) was added at ambient temperature for 1 hour. After necessary washing and overnight freeze-drying, Ce6@ZIF-8-PDA/UBI was obtained. The calculation of Ce6 loading efficiency was based on the following formula: (Corresponding Ce6@ZIF-8 weight×LE Ce6@ZIF-8 )/Ce6@ZIF-8-PDA/UBI weight×100%. To investigate whether UBI was grafted on the final nanoparticles, Cy5.5-labeled UBI was used, and fluorescence images were acquired via confocal laser scanning microscopy (CLSM, TCS SP8). Characterization of Ce6@ZIF-8-PDA/UBI The morphologies of the nanoparticles were examined by transmission electron microscopy (TEM, HT-7800, Hitachi, Japan). For dynamic light scattering (DLS) measurements, a Malvern Zetasizer Nanoseries (Nano ZS90, Nano-ZS 90, Malvern Instrument, United Kingdom) was used. Fourier transform infrared (FT-IR) spectroscopy was performed using a Nicolet 550 spectrophotometer. X-ray diffraction (XRD) analysis was conducted using a Bruker D8 Advance X-ray diffractometer (Bruker AXS, Germany). A surface area and porosity analyzer (Micromeritics Tristar 3020, USA) was utilized to assess the nitrogen adsorption-desorption properties. Analysis of ROS generation To evaluate ROS generation, we employed an electron spin resonance (ESR) spectrometer (JEOL-FA200, Japan) to record ESR spectra. This assessment involved treatments with or without laser irradiation (808 nm, 5 minutes, 1.3 W/cm²) in the presence of 2,2,6,6-tetramethylpiperidine (TEMP) as a spin trap agent to capture ROS. Moreover, we used 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic indicator to analyze ROS generation in Ce6@ZIF-8-PDA/UBI nanoparticles upon 808 nm laser irradiation. Briefly, a solution consisting of 4 mM TMB and 100 µg/mL Ce6@ZIF-8-PDA/UBI was subjected to irradiation using an 808 nm laser at various power densities (0, 0.6, 1.3, and 2.0 W/cm²) for 5 minutes. Alternatively, the same solution was exposed to the laser for varying durations (0, 1, 3, 5, 7, and 9 minutes) while maintaining a constant power density of 1.3 W/cm². Furthermore, we investigated the photothermal characteristics of Ce6@ZIF-8-PDA/UBI solutions in PBS at different concentrations (0, 100, 200, 300, 400, and 500 µg/mL) under NIR irradiation (5 minutes, 808 nm, 1.3 W/cm²). After irradiation, 100 µL of each solution above was dispensed into a 96-well microplate and subsequently analyzed using a microplate reader (Spark 10M, TECAN, Switzerland) following photograph recording. NIR photothermal performance The photothermal properties of the prepared nanosystems were evaluated by using an infrared thermal camera (Fotric 226S, Fotric Inc., China). Real-time temperature monitoring and thermal imaging were conducted to obtain detailed temperature elevation profiles for various nanoparticle compositions, including ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI (all at 200 µg/mL). These measurements were taken under controlled laser irradiation conditions at 808 nm with a power density of 1.3 W/cm². Furthermore, temperature elevation profiles of Ce6@ZIF-8-PDA/UBI nanoparticles (200 µg/mL) under various power densities (0, 0.6, 1.3, and 2.0 W/cm²) of 808 nm laser irradiation were also recorded. Likewise, different concentrations (100, 200 and 400 µg/mL) of Ce6@ZIF-8-PDA/UBI aqueous solutions were systematically studied under constant laser irradiation conditions (808 nm, 1.3 W/cm²). Additionally, a comprehensive assessment of the thermal properties of Ce6@ZIF-8-PDA/UBI nanoparticles in PBS (200 µg/mL) was performed. The solution underwent successive cycles of 5 minutes of laser irradiation (808 nm, 1.3 W/cm²) followed by natural cooling to 28.7°C. The photothermal conversion efficiency of the Ce6@ZIF-8-PDA/UBI nanoparticles was calculated using the following equation according to a previous study [ 28 ]. $$\\eta =\\frac{hS({T}_{max}-{T}_{suur})}{\\text{I}(1-{10}^{-{A}_{808}})}$$ where T max is the maximum temperature of the Ce6@ZIF-8-PDA/UBI solution, Tsuur is the ambient temperature, and A is the absorbance of the Ce6@ZIF-8-PDA/UBI solution at 808 nm (A 808 = 0.1522). The hS was calculated using the following equation: $$hS=-\\frac{{\\sum }_{i}{m}_{i}{\\text{C}}_{i}}{{\\tau }_{s}}$$ where m = 0.3 g, c = 4.2 J/g, and τs is the slope of the fitting line between cooling time t and -ln θ : $$\\theta =\\frac{T-{T}_{suur}}{{T}_{max}-{T}_{suur}}({\\tau }_{s}=139.1)$$ Synergistic antibacterial activity of PTT and PDT in vitro Bacterial aggregation and targeting First, S. aureus was cultured overnight in LB at 37°C. The culture was then concentrated at 5000 rpm for 5 minutes and transferred to PBS. Subsequently, the bacterial mixture was kept stationary and exposed to Cy5.5-labeled ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles. The plates were incubated at 37 ℃ for 2 hours. The bacteria were then concentrated and subjected to three washes with PBS before being stained with SYTO9 dye. The resultant aggregated bacterial samples were observed using CLSM (TCS SP8, Leica, Germany). To investigate bacterial targeting and substantiate the binding between nanoparticles and bacteria, the samples were diluted, resuspended, and analyzed using CLSM and scanning electron microscopy (SEM, Hitachi, S4800). Plate counting Coculturing involved a 1 mL aliquot of bacterial suspensions ( S. aureus, E. coli , 2×10 8 colony-forming units (CFU)/mL) in PBS buffer (0.01 M, pH 7.4) supplemented with 1 mL of various nanoparticles (ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI) at 37°C for 2 hours. The bacteria in the NIR + groups were irradiated with an 808 nm laser (1.3 W/cm 2 ) for 5 minutes, while those in the NIR- groups remained untreated. After coculturing, all bacteria were diluted and cultured on LB plates for 18 hours at 37°C. The antibacterial efficacy of each group was evaluated by photographing and quantifying the CFUs. Oral bacteria, including F. nucleatum and P. gingivalis , were also investigated similarly. Live/dead bacterial fluorescence assays After applying different samples to the bacterial suspension, following centrifugation and washing with PBS, a mixture of propidium iodide (PI) and SYTO9 dye (1 µL) (Invitrogen Detection Technologies, USA) was added. This blend was subsequently incubated in darkness at room temperature for 15 minutes. Due to the different integrity of the bacterial cell membranes, all bacteria could be labeled with green fluorescence by SYTO9. In contrast, only dead bacteria could be marked explicitly with red fluorescence by PI. Finally, CLSM (Leica TCS SP8) was used for cell imaging. SEM and TEM imaging Next, the bacterial suspensions containing S. aureus and E. coli were centrifuged and fixed, and the bacterial morphology was examined and visualized via SEM imaging (S4800, Hitachi, Japan) and TEM imaging (HT-7800, Hitachi, Japan). Synergistic antibiofilm activities of PTT and PDT in vitro Biofilm penetration P. gingivalis was cultured overnight in BHI medium at 37°C, followed by dilution with the medium. The bacterial suspension was placed in a 6-well plate containing sterile coverslips (18 × 18 mm). The coverslips were vertically positioned and subjected to static cultivation at 37°C for 48 hours. After the formation of mature biofilms on the coverslips, the media were removed, and the biofilms were washed three times with sterile PBS buffer to isolate the planktonic bacteria effectively. The biofilms were then exposed to distinct Cy5.5-labeled particles in suspension (200 µg/mL) for 2 hours, during which they were gently agitated (50 rpm). After this exposure period, the biofilms were rinsed with PBS to eliminate any free particles. Subsequently, the biofilms were stained with FITC-labeled concanavalin A (FITC-ConA) and finally subjected to CLSM imaging. Biofilm survival In the biofilm survival assay, the biofilms were subsequently exposed to various particles in suspension (200 µg/mL). Following a 2-hour coculturing period with gentle agitation (50 rpm) at 37 ℃, the biofilms in the light irradiation groups were exposed to an 808 nm laser (1.3 W/cm 2 ) for 5 minutes. After this irradiation, the biofilms were washed with PBS to eliminate any free particles and then subjected to staining with PI and SYTO9 dye following the manufacturer's instructions. Finally, the biofilms were imaged using CLSM. In vivo infection control and the infected tissue repair To confirm the in vivo antibacterial effect of the synthesized nanosystems, a mouse cutaneous wound infection model and a rat femur peri-implantitis model were selected. All the animal surgical experiments performed in this research were approved by the Animal Ethics Committee of Shanghai Ninth People’s Hospital affiliated with Shanghai Jiao Tong University School of Medicine. Mouse cutaneous wound infection model A full-thickness skin defect model with S. aureus infection was established using 8-week-old Kunming mice. Initially, a sterile scalpel was utilized to create a skin defect measuring approximately 10 mm in diameter. Subsequently, 100 µL of S. aureus solution (1×10 8 CFU/mL) in LB was introduced into the wound. Following a 24-hour postinfection period, the animals were randomly assigned to four groups (3 per group). Subsequently, 200 µL of aqueous solution containing 200 µg/mL ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, or Ce6@ZIF-8-PDA/UBI was individually applied to the wound site. On both days 1 and 3 within each group, the infected wound sites of the animals underwent irradiation with an 808 nm NIR laser (1.3 W/cm², 5 minutes). On the third day, samples were collected from the wound site and treated with bacteria incubation for 24 h at 37°C. Afterward, the bacterial suspensions were collected, and the OD600 was determined by using a microplate reader (Spark 10M, TECAN, Switzerland). On the 14th day, skin tissue encompassing the wound area was collected for subsequent histological analysis, including hematoxylin and eosin (HE) staining and Masson's trichrome staining. Within 14 days postsurgery, the macroscopic appearance and dimensions of the infected wound were documented at different time points through digital photography, employing a ruler for reference. On the 14th day, skin tissue encompassing the wound area was collected for subsequent histological analysis, including HE staining and Masson's trichrome staining. In vivo peri-implant infection model To further validate the effectiveness of the modified nanoparticles against peri-implant infection, a rat femur peri-implantitis model was established. The distinct titanium implants were immersed in a solution of inoculated S. aureus bacteria (2×10 3 CFUs) to cultivate bacterial biofilms adhering to the implant surface. These implants were subsequently placed in suspensions of various modified nanoparticles for 2 hours. Prior to the procedure, male SD rats (8 weeks old) were anesthetized. The femur near the knee joint was exposed through an incision, and a narrow channel was created at the femoral condyle using a surgical drill. The animals were randomly categorized into the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI groups, and each animal received an implant featuring nanoparticle modifications. The subsequent steps involved careful suturing of the skin and soft tissue. On both days 1 and 3 within each group, each infected wounds underwent irradiation with an 808 nm NIR laser (1.3 W/cm², 5 minutes). After 14 days of implantation, tissues surrounding the infected implant site were extracted for HE staining. This evaluation aimed to gauge the in vivo antibiofilm efficacy of different nanoparticles. Additionally, major organs were collected and subjected to HE staining to assess potential in vivo toxicity linked to the nanoparticles employed in the study. CCK-8 viability assay The cell viability assessment of the prepared nanoparticles was conducted through a CCK-8 viability assay. L929 cells were seeded within 96-well plates at a density of 1×10 4 cells/well and allowed to adhere overnight at 37°C in an atmosphere of 5% CO 2 and 95% air. Subsequently, the cells were exposed to the prepared ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles at various concentrations (0, 10, 50, 100, 200, 300, 400 and 500 µg/mL) for 24 hours. Following this incubation, each well was supplemented with 10 µL of CCK8 reagent (BestBio, Shanghai, China) and then incubated in the dark at 37°C for 1.5 hours. The optical density of each well was subsequently assessed at 450 nm using a microplate reader (Spark 10M, TECAN, Switzerland). Hemolytic assay Various concentrations of Ce6@ZIF-8-PDA/UBI solutions (0.8 mL in PBS) were mixed with 0.2 mL of the collected PBS-diluted RBCs. The mixture was then cultured at room temperature for 4 hours. Afterward, the supernatant was collected through centrifugation, and the absorbance at 545 nm was measured using a microplate reader (Spark 10M, TECAN, Switzerland). Finally, the hemolysis ratio was calculated using the following equation: Hemolysis (%) = (OD Ce6@ZIF-8-PDA/UBI -OD PBS )/(OD ddwater -OD PBS ) × 100%. Statistical analysis All data points were expressed as the mean ± standard deviation (SD). The t-test and one-way analysis of variance (ANOVA) were used to compare values among groups. A p value < 0.05 was considered to indicate statistical significance. All the data analysis were conducted with SPSS Statistics 24 software. Results Synthesis and characterization of nanoparticles The microstructures of ZIF-8 and ZIF-8-PDA were assessed via TEM, as shown in Fig. 1 a. The ZIF-8-PDA nanoparticles retained the original polyhedral shape of the ZIF-8 nanoparticles and displayed an approximate size of 100 nm. An obvious dark black layer could be found on the surface of the ZIF-8-PDA nanoparticles, which might be attributed to the PDA surface modification. Ce6@ZIF-8-PDA/UBI has a morphology similar to that of ZIF-8-PDA (Fig. S1 ). The FT-IR spectra of ZIF-8-PDA confirmed the presence of a PDA shell, where the stretches at 1486 cm − 1 and 1260 cm − 1 correspond to the phenolic N-H and C-O of PDA, respectively (Fig. S2). DLS analysis (Fig. 1 b) revealed that the size of the ZIF-8-PDA nanoparticles (93.8 ± 12.6 nm) was slightly greater than that of the ZIF-8 nanoparticles (90.1 ± 13.9 nm). A comparison of the XRD patterns of different nanoparticles (Fig. S3) implied that the introduction of PDA, Ce6, and UBI preserved the crystal structure of the ZIF-8 nanoparticles. The introduction of PDA, Ce6, and UBI led to a significant reduction in the intensity of the diffraction peaks. This attenuation was attributed to the external shielding effects of PDA and UBI and the internal placeholder effect of Ce6. The characteristic nitrogen adsorption-desorption isotherms for ZIF-8, ZIF-8-PDA, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI confirmed the porous properties of the particles (Fig. 1 c). All samples displayed a type I isotherm, with a steepness in the low-pressure range (P/P 0 = 0 to 0.1) indicating the presence of micropores. In contrast to those of ZIF-8, the isotherms of Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI showed reduced N 2 adsorption. This substantiated the successful modification of the ZIF-8 surface and Ce6 loading within the micropores. The Ce6 loading efficiency of Ce6@ZIF-8-PDA/UBI reached 47.86%±2.68%. According to the fluorescence images (Fig. S4), the red signal of Cy5.5-labeled UBI could be verified in the Ce6@ZIF-8-PDA/UBI groups, which confirmed the successful grafting of UBI onto the nanoparticles. ROS generation capacity By employing ESR spectroscopy to identify the irradiation product of Ce6@ZIF-8-PDA/UBI triggered by NIR, TEMP was employed as a trapping probe for ROS. The spectral data in Fig. 1 d show the NIR-induced generation of highly reactive singlet oxygen ( 1 O 2 ) from Ce6@ZIF-8-PDA/UBI. A characteristic three-line spectrum of TEMP/ 1 O 2 with a balanced intensity of 1:1:1 was obtained. Conversely, Ce6@ZIF-8-PDA/UBI without NIR irradiation exhibited nearly no TEMP/ 1 O 2 signals under the same conditions. When subjected to NIR irradiation, the ROS generation capacity of the Ce6@ZIF-8-PDA/UBI nanoparticles was assessed using a TMB chromogenic reaction (Fig. 1 e-g). The TMB solution underwent oxidation by 1 O 2 produced by Ce6@ZIF-8-PDA/UBI nanoparticles under NIR irradiation, transitioning from colorless to blue, with two distinct absorption peaks emerging at 370 and 650 nm. The evaluation of 1 O 2 production was investigated under different conditions including various concentrations (0, 100, 200, 300, 400, and 500 µg/mL) of Ce6@ZIF-8-PDA/UBI nanoparticles, different power densities of 808 nm laser irradiation (0, 0.6, 1.3, and 2.0 W/cm 2 ), and various durations (0, 1, 3, 5, 7, and 9 min). Initial analysis revealed a distinct reliance of NIR-triggered 1 O 2 production by Ce6@ZIF-8-PDA/UBI on the irradiation power density. The color deepening in Fig. 1 e accompanied the increase in power density, and the absorption peak displayed a corresponding trend. Without NIR irradiation, negligible 1 O 2 formation was observed. Furthermore, as shown in Fig. 1 f-g, 1 O 2 production by Ce6@ZIF-8-PDA/UBI exhibited a positive correlation with irradiation time and nanoparticle concentration. NIR photothermal capacity As shown in Fig. 2 a and b, the temperature variations of the Ce6@ZIF-8-PDA solution and Ce6@ZIF-8-PDA/UBI solution upon 808 nm light irradiation increased over time. In contrast, the PBS, ZIF-8, and Ce6@ZIF-8 solutions did not significantly increase the temperature. Notably, the Ce6@ZIF-8-PDA solution reached 48.4 ℃ after 5 minutes of irradiation at 1.3 W/cm 2 . Similarly, the temperature of the Ce6@ZIF-8-PDA/UBI solution reached 47.2 ℃, indicating that the addition of UBI had minimal impact on the photothermal effect of Ce6@ZIF-8-PDA. The thermal performance test (Fig. 2 c and d) revealed that at a nanoparticle concentration of 200 µg/mL and an irradiation power of 1.3 W/cm 2 , the temperature of the Ce6@ZIF-8-PDA/UBI solution increased from 23.0 ℃ to 47.2 ℃ within 5 minutes. As the irradiation power increased from 0.6 W/cm 2 to 1.3 W/cm 2 , the final solution temperature increased by approximately 8.7°C. However, when the power was further increased to 2 W/cm 2 , the temperature further increased by 8.9°C. Notably, with an elevated nanoparticle concentration of 400 µg/mL and a power of 1.3 W/cm 2 , the temperature of the particle solution increased to 50.7 ℃ after 5 minutes of irradiation. Subsequently, the photothermal stability of the Ce6@ZIF-8-PDA/UBI nanoparticles was evaluated through a comprehensive photothermal performance cycle. As exemplified in Fig. 2 e, the temperature profiles exhibited remarkable resilience after five cycles of alternating laser activation and deactivation. As shown in Fig. 2 f and g, the calculated photothermal conversion efficiency for Ce6@ZIF-8-PDA/UBI was 22.43%. In vitro antibacterial effect of synergistic PDT/PTT activities To evaluate the influence of nanoparticles on bacterial binding and aggregation, S. aureus was incubated with Cy5.5-labeled nanoparticles, including ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI. As shown in Fig. 3 a, a discernible aggregation of S. aureus , denoted by the green fluorescence of SYTO9 dye, occurred upon exposure to nanoparticles featuring a PDA coating, including Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI nanoparticles. This outcome was attributed to the multivalent interactions between the nanoparticles and S. aureus cell walls facilitated by the presence of the PDA layer. Notably, the introduction of UBI further potentiated bacterial aggregation, surpassing the effect of PDA alone. Upon dilution and resuspension, CLSM visualization (Fig. 3 b) of S. aureus treated with Ce6@ZIF-8-PDA/UBI nanoparticles revealed that the presence of green fluorescent clusters closely correlated with the distribution of red fluorescent dots along the surface and edges of the particles, resulting in overlapping areas exhibiting yellow fluorescence. Virtually all green fluorescently labeled bacteria exhibited dense red fluorescent material enveloping them. In contrast, the ZIF-8- and Ce6@ZIF-8-treated bacteria showed nearly no red particle adhesion. In the SEM images, adhered nanoparticles could also be clearly found on the surface of the bacteria in the Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI groups. Ce6@ZIF-8-PDA/UBI showed more aggregation on S. aureus than did Ce6@ZIF-8-PDA. Figure 4 a and c illustrates the CFU counts of S. aureus and E. coli after incubation with different nanoparticles. There were no significant discrepancies in CFU counts without NIR irradiation. In contrast, upon NIR exposure, substantial reductions in CFU counts were evident for S. aureus and E. coli treated with Ce6@ZIF-8-PDA (Group III) and Ce6@ZIF-8-PDA/UBI (Group IV), with the latter exhibiting more potent antibacterial effects. To further validate the in vitro antibacterial efficacy of the NIR-activated nanoplatforms against S. aureus and E. coli , live/dead fluorescence staining assays were employed. Consistent with the results of the plate counting experiments, the absence of NIR treatment resulted in predominantly green-stained bacteria, indicating their viability (Fig. 4 b and d). Conversely, NIR-treated Ce6@ZIF-8 (Group II), Ce6@ZIF-8-PDA (Group III), and Ce6@ZIF-8-PDA/UBI (Group IV) displayed a progressive increase in yellow signals resulting from the overlap of green and red fluorescence. This trend indicated heightened antibacterial activity, most prominently observed in the NIR-activated Ce6@ZIF-8-PDA/UBI group. Subsequently, the antibacterial impact of the distinct nanoparticles was qualitatively assessed through SEM and TEM analysis. As shown in Fig. 4 b and d, the bacterial skeleton structures within the Ce6@ZIF-8-PDA/UBI group appeared dispersed and collapsed, accompanied by bacterial surface wrinkling, distortion, and even complete dissolution. In vitro synergistic PDT/PTT activities against oral bacteria and oral biofilms The antibacterial activity of the distinct biomaterials against F. nucleatum and P. gingivalis was further investigated using the standard plate counting method. As shown in Fig. 5 a and b, no significant reductions were observed across the various groups without NIR treatment. Notably, the most pronounced antibacterial effect was evident in the Ce6@ZIF-8-PDA/UBI group (Group IV) after NIR treatment, highlighting the efficient antibacterial property of the particle system. The bacterial survival rate for different nanoparticles without irradiation (NIR- groups) remained at nearly 100%. However, upon irradiation (NIR + groups), the bacterial survival rate in the Ce6@ZIF-8 group (Group II) significantly decreased compared to that in the ZIF-8 group (Group I). Specifically, the bacterial survival rates after Ce6@ZIF-8 treatment reached 71.1%±0.9% and 73.0%±2.0% for F. nucleatum and P. gingivalis , respectively. This finding suggested that Ce6@ZIF-8-based PDT and PTT exhibited a moderate antibacterial effect on planktonic bacteria but could not eliminate bacteria at the safe concentrations utilized. However, the combination of PDA coating and Ce6 loading (Group III: Ce6@ZIF-8-PDA) led to a more substantial reduction in the bacterial count, nearly 70%, for both F. nucleatum and P. gingivalis . This finding underscores the exceptional in vitro antibacterial activity arising from the synergistic action between Ce6 loading and the PDA layer within the nanosystem. Furthermore, the Ce6@ZIF-8-PDA system modified with UBI (Group IV: Ce6@ZIF-8-PDA/UBI) nearly eradicated all bacteria, including both F. nucleatum and P. gingivalis . In conclusion, the Ce6@ZIF-8-PDA/UBI nanoplatforms exhibited remarkable antibacterial activity through combined PDT and PTT. The exploration of nanoparticle penetration within biofilms involved examining formed P. gingivalis biofilms stained with FITC-ConA. These biofilms were subsequently exposed to suspensions containing Cy5.5-labeled ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoplatforms, followed by comprehensive imaging through CLSM 3D visualization (Fig. 5 c). Remarkably, the inclusion of PDA and UBI led to the most profound penetration by Cy5.5-labeled Ce6@ZIF-8-PDA/UBI within the biofilms, surpassing all other groups. This was evidenced by the uniform and vibrant distribution of red fluorescence arising from particles throughout the biofilm, extending even to its bottom layers. In stark contrast, the extent of Ce6@ZIF-8 penetration within the biofilm markedly decreased, signifying restricted penetration due to the absence of PDA, which hindered the adhesion and penetration of Ce6@ZIF-8 into the biofilm. The incorporation of PDA and UBI on the surface coating significantly enhanced the adhesion and targeting capabilities of the nanoplatform to the biofilm matrix. Consequently, this enhancement facilitated substantial penetration into the biofilm structure, leading to the accumulation of noticeable concentrations of Cy5.5-labeled nanoplatforms [ 29 – 31 ]. For a comprehensive evaluation of the antibiofilm capabilities of the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoplatforms under various conditions (including with or without NIR treatment, 808 nm, 5 min, 1.3 W/cm 2 ), a dual-staining approach involving PI and SYTO9 dye was employed. This approach allowed for the simultaneous visualization of live and dead cells within biofilms. The results were captured and analyzed using CLSM 3D imaging (Fig. 5 d and e). Figure 5 d shows biofilms in their intact state without NIR irradiation across all groups, exhibiting intense green fluorescence. In contrast, Fig. 5 e illustrates a shift in the response, with the NIR-irradiated ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI groups displaying decreased green fluorescence and increased red fluorescence. Notably, the NIR-activated Ce6@ZIF-8-PDA/UBI group exhibited the most prominent bactericidal effect on P. gingivalis biofilms. Collectively, these comprehensive findings underscore the robust antibacterial properties of Ce6@ZIF-8-PDA/UBI nanoparticles, especially when harnessed by NIR activation. These findings emphasize the potential of these nanoparticles for future applications in combating bacterial infections. The exceptional light-driven antibiofilm activity of Ce6@ZIF-8-PDA/UBI is likely a result of the efficient bacterial localization mediated by PDA/UBI and the PDT/PTT facilitated by Ce6/PDA interactions. In vivo study Treatment of S. aureus infected skin wound healing With the promising in vitro antibacterial outcomes established, an investigation into the in vivo antibacterial efficacy of different nanoparticles was carried out on a full-thickness skin defect model with S. aureus infection. As shown in Fig. 6 a, temperature fluctuations around the wound site during NIR light irradiation in the presence of Ce6@ZIF-8-PDA/UBI were apparent. A mere 5-minute session of NIR irradiation caused the wounds treated with Ce6@ZIF-8-PDA/UBI to experience a swift temperature increase from 32.0 to 47.9°C. This rapid increase underlines the pronounced in vivo PDT effect of Ce6@ZIF-8-PDA/UBI, showing its precise localization at the wound site. In contrast, the PBS NIR + group exhibited only a marginal temperature change from 32.0 to 34.6 ℃, underscoring the distinct specificity and efficacy of the nanocomposites. From the planktonic growth of bacteria in samples collected from the infected wound site after NIR irradiation treatment, we could see that Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI nanoparticles showed significant effective wound antibacterial therapy among the four treatments (Fig. 6 b). Images of wound repair at various time points (1, 3, 7, and 14 days) were taken, as shown in Fig. 6 c. In comparison, the corresponding dynamics in the wound areas are graphically presented in Fig. 6 d. Wound healing rates increased over time across all groups. However, compared with those in the other groups, the healing pace in the NIR-treated Ce6@ZIF-8-PDA/UBI group (group IV) markedly accelerated, with the number of infected wounds nearly vanishing by day 14 (Fig. 6 e). Deeper insights into the healing process were obtained through histological analysis of the surrounding wound tissues. As shown in Fig. 6 f, both the ZIF-8 and Ce6@ZIF-8 groups (Groups I and II) exhibited substantial numbers of neutrophils within the skin tissue, indicating persistent bacterial infection. Moreover, by day 14, these groups showed incomplete epidermal structures, accompanied by considerable defects. In contrast, the Ce6@ZIF-8-PDA group (Group III) exhibited notable fibroblast migration, albeit with incomplete epithelialization (Fig. 6 f). Most impressively, the Ce6@ZIF-8-PDA/UBI group displayed a significant reduction in inflammation, with both epidermal and dermal structures nearly intact. This finding suggested superior wound healing efficiency. The results were supported by Masson's trichrome staining, which showed that by day 14, the Ce6@ZIF-8-PDA/UBI group displayed the most significant accumulation of collagen fibers (Fig. 6 f). In summary, the experimental results underscore the remarkable efficacy of Ce6@ZIF-8-PDA/UBI treatment coupled with NIR irradiation in repairing full-thickness skin defects and S. aureus infections in vivo. In vivo peri-implant infection model To further substantiate the impact of Ce6@ZIF-8-PDA/UBI nanoparticles on peri-implant infection, a rat femur peri-implantitis model was established. HE staining revealed substantial infiltration of inflammatory cells, including monocytes, neutrophils, and eosinophils, into the soft tissue in both the ZIF-8 and Ce6@ZIF-8 groups (Fig. 7 ). Conversely, the Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI groups exhibited only sparse occurrences of monocytes, neutrophils, and eosinophils (Fig. 7 ). This observation implies a moderate inflammatory response and successful antibacterial efficacy. Consequently, in vivo , under 808 nm NIR irradiation, the Ce6@ZIF-8-PDA/UBI nanoparticles demonstrated the most potent antibacterial effects. Biosafety Assessment The cytotoxicity of the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles to L929 cells was assessed using the CCK assay (Fig. 8 a). The cells were exposed to various concentrations of nanoparticles (10, 50, 100, 200, 300, 400, and 500 µg/mL) for 24 hours. Analysis of cell viability revealed that cell survival rates exceeded 80% for concentrations lower than or equal to 400 µg/mL (which surpassed the working concentration), indicating minimal toxicity of the carriers to L929 cells. These findings underscore the favorable biocompatibility of PDA-modified and UBI-loaded nanoparticles, suggesting their promising potential for drug delivery aimed at eradicating oral biofilms. Addressing potential nanoparticle toxicity remains a critical concern within the medical community and is closely linked to the safe clinical utilization of nanomaterials. In this study, hemolysis assays were conducted to provide additional insight into the impact of the prepared nanosystems on RBCs. As shown in Fig. 8 b, the supernatant exhibited a vibrant red hue when suspended in deionized water, while the PBS groups (0 µg/mL) retained their transparent appearance. The supernatant was transparent at particle concentrations of 10, 50, 100, 200, 300, 400, and 500 µg/mL. There was no particle concentration-induced hemolysis rate greater than 5%. These findings indicated that the particles developed in this study are compatible when they are used at concentrations ranging from 0-500 µg/mL. Following the implantation of titanium implants bearing bacterial biofilms and subsequent treatment with NIR-irradiated ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles, histological examination via HE staining of major organs (heart, liver, spleen, lung, and kidney) within a rat femur peri-implantitis model was performed. The analysis aimed to ascertain the presence of any discernible abnormalities in the major organs of rats subjected to various nanoparticle treatment (Fig. 8 c). The results indicated the absence of conspicuous anomalies, reinforcing the favorable potential of Ce6@ZIF-8-PDA/UBI nanoparticles for prospective clinical applications. Discussion The challenges posed by bacterial biofilm-associated infections are substantial in healthcare due to their heightened resistance to conventional antimicrobial agents. Recently, increased attention has been directed toward creating novel nanosystems designed to target bacteria within biofilms and disrupt the structural integrity of these biofilms. Nanoparticles offer several advantages, such as the ability to penetrate the biofilm matrix, direct targeting of bacterial cells within the biofilm, enhanced therapeutic outcomes, and reduced side effects. This study introduces an innovative approach, the Ce6@ZIF-8-PDA/UBI system, which achieves precise bacterial targeting and subsequent effective bacterial eradication through the synergistic application of both PDT and PTT. The strong adhesion of Ce6@ZIF-8-PDA/UBI to oral biofilms stems from the incorporation of PDA. PDA, a polymer akin to mussel attributes, is recognized for its robust adhesion owing to its diverse cationic amino acids [ 32 ]. Furthermore, PDA exhibits zwitterionic characteristics, with amine and phenolic hydroxyl groups juxtaposed to create positive charges at lower pH and negative charges at higher pH. Consequently, PDA-modified nanomaterials show an enhanced affinity for bacterial adsorption [ 33 ]. For example, it has been reported that carboxymethyl chitosan/sodium alginate hydrogels coated with PDA can effectively eliminate biofilms and multidrug-resistant bacteria, aiding in wound healing [ 34 ]. Another study harnessed the inherent self-attaching ability of PDA to enhance biofilm lysis and bacterial elimination in S. aureus biofilms grown on titanium substrates [ 35 ]. PDA offers additional benefits, such as facile preparation, functionalization, biocompatibility, and excellent photothermal conversion efficiency. As an infrared-sensitive molecule, PDA has been employed to establish multifunctional nanoplatforms, yielding improved photothermal effects for bacterial and biofilm eradication [ 36 ]. Consistently, it has been shown that a PDA coating enhances ZIF-8 stability and dispersion while providing high photothermal conversion efficiency [ 37 ]. The Ce6@ZIF-8-PDA/UBI nanosystem achieved outstanding antimicrobial performance due to its remarkable bacterial targeting capabilities. Various methods are employed for targeting bacteria, including antibodies, aptamers, and peptides. Antibodies are known for their high specificity and affinity for target antigens, but they often lack robust therapeutic efficacy [ 1 ]. Aptamers, while offering advantages such as low cytotoxicity, ease of preparation, and precise targeting abilities, face limitations due to the scarcity of available marketed products and potential instability in vivo . On the other hand, peptides stand out as exceptional targeting agents in the battle against infections because of their straightforward synthesis and remarkable specificity [ 38 ]. Peptides occupy a middle ground between antibodies and small molecular ligands, granting them a substantial binding area with receptors. This translates into significantly enhanced specificity and binding affinity compared to their molecular counterparts. Notably, antibacterial peptides execute their antibacterial functions through diverse strategies, such as disrupting peripheral membrane proteins, augmenting cell membrane permeability, and disrupting cell membrane organization. Nonetheless, challenges such as hemolytic toxicity, low protease stability, and a confined contact surface area somewhat hamper the potential applications of these materials. To address these challenges, the conjugation of peptides with nanoparticles has emerged as an exceptionally effective strategy [ 39 ]. To bolster bacterial targeting in this study, we incorporated UBI, an AMP-derived peptide renowned for its affinity and specificity for bacterial cell membranes [ 40 ]. Studies have shown that antibacterial peptides can target bacteria and induce bacterial cell membrane disruption to exert bactericidal effects [ 41 ]. Consequently, the UBI peptide has been utilized to target bacterium-infected sites, improving therapeutic outcomes [ 42 ]. An additional attribute of the Ce6@ZIF-8-PDA/UBI system lies in its integration of both PDT and PTT modalities. PDT harnesses PSs to generate ROS, initiating bacterial eradication through membrane and DNA disruption. On the other hand, PTT employs photothermal agents to induce localized hyperthermia, achieving sterilization by denaturing bacterial proteins and causing irreversible bacterial damage [ 43 ]. While PDT and PTT each exhibit individual efficacy, their combined utilization enhances antibacterial potency. Thus, incorporating synergistic PDT/PTT effects offers a viable strategy for enhancing antibacterial efficiency [ 44 ]. In our research, we proposed the utilization of ZIF-8 nanoparticles loaded with the photosensitizer Ce6, integrating PDT and PTT for bacterial infection eradication. TEM analysis revealed that after Ce6@ZIF-8-PDA/UBI was subjected to NIR irradiation, the bacterial cell membranes were distorted, shrunken, severely damaged, or wholly disrupted, resulting in qualitative alterations to the cytoplasmic contents. These morphological anomalies appeared more pronounced than those observed with isolated PTT or PDT treatments. Additionally, live/dead staining corroborated these findings, with the most intense red fluorescence observed in the Ce6@ZIF-8-PDA/UBI/NIR + group, indicating significant compromise of bacterial cell membrane integrity, accompanied by damage and shrinkage. Based on these observations, we deduced that the antibacterial effect of Ce6@ZIF-8-PDA/UBI can be attributed to the generation of thermal and chemical energy. This energy disrupts the structural integrity of the cell membrane, triggers an increase in ROS within the bacteria, and results in cytoplasmic content leakage. Ultimately, these processes lead to loss of bacterial function and even bacterial death. Several investigations have also provided novel insights into the underlying antibacterial mechanism. PDT and PTT can expedite the transition of macrophages from the proinflammatory (M1) phenotype to the anti-inflammatory (M2) phenotype, implying that prevention of microbial invasion may involve both direct biofilm eradication via ROS and activation of the host immune response [ 45 ]. Furthermore, research has demonstrated that mild PTT (< 45°C) can induce heat shock proteins (HSPs), some of which play a crucial role in stimulating antigen-producing cells such as dendritic cells (DCs). This stimulation enhances the host immunological response, thereby facilitating tissue healing [ 46 ]. Thus, the potential immune responses underlying the Ce6@ZIF-8-PDA/UBI-mediated antibacterial process should be studied in the future. A diverse range of bacterial strains were subjected to antibacterial experiments in this study. Initially, we showed the effective defense of Ce6@ZIF-8-PDA/UBI nanoparticles against infections caused by both gram-positive ( S. aureus ) and gram-negative bacteria ( E. coli ). Subsequently, to further substantiate the potential of Ce6@ZIF-8-PDA/UBI for oral biofilm elimination, we assessed its impact on P. gingivalis and F. nucleatum , which are prominent bacterial species within the periodontal pocket. A series of experimental results consistently indicated the remarkable antibacterial properties of Ce6@ZIF-8-PDA/UBI both in vitro and in vivo . In our study, the superior antibacterial efficacy of the Ce6@ZIF-8-PDA/UBI system can be attributed to its adhesive properties, precise targeting of bacteria, and synergistic potential for PDT/PTT. The Ce6@ZIF-8-PDA/UBI system established in this study not only demonstrated robust antibacterial and biofilm resistance effects but also ensured the safety of the surrounding cells and tissues. CCK8 assays and HE staining of major organs (heart, liver, spleen, lung, and kidney) confirmed that the concentration of Ce6@ZIF-8-PDA/UBI utilized in our study met the cytotoxicity requirements. Notably, the Ce6@ZIF-8-PDA/UBI nanoparticles made their impact on only biofilms, limiting their toxicity to localized regions and inducing minimal photoinduced damage. Moreover, the photothermal temperature of this nanoparticle system, ranging from 38.5 to 56.1 ℃, could be regulated to be lethal for bacteria while remaining harmless to adjacent tissues. The Ce6@ZIF-8-PDA/UBI developed in this study holds significant potential as an effective antibacterial system for clinical applications. Conclusion In summary, using a synergistic approach involving PDT and PTT, we have successfully devised a novel Ce6@ZIF-8-PDA/UBI nanosystem designed to combat bacterial infections and eradicate biofilms. This inventive strategy enables precise bacterial targeting and enhanced penetration into oral biofilms. The combination of PDT and PTT potently inhibits biofilms while minimizing harm to organisms. Thus, this versatile system holds significant promise as a solution for tackling persistent biofilm infections. Abbreviations EPSs Extracellular polymeric substances PDT Photodynamic therapy ROS Reactive oxygen species Ce6 Chlorin e6 ZIF Zeolitic imidazolate framework PTT Photothermal therapy PDA Polydopamine NIR Near-infrared UBI Ubiquicidine MOF Metal-organic framework HMIM 2-methylimidazole LE Loading efficiency CLSM Confocal laser scanning microscopy TEM Transmission electron microscopy DLS Dynamic light scattering FT-IR Fourier transform infrared XRD X-ray diffraction ESR Electron spin resonance TEMP 2,2,6,6-tetramethylpiperidine TMB 3,3',5,5'-tetramethylbenzidine SEM Scanning electron microscopy CFU Colony-forming units PI Propidium iodide FITC-ConA FITC-labeled concanavalin A HE Hematoxylin and eosin SD Standard deviation HSPs Heat shock proteins DCs Dendritic cells Declarations Author contributions W.S., A.Z., X.W. and L.C. designed the research strategy. A.Z., X.W. and L.C. performed the materials construction and characterizations. W.S., A.Z., and X.W. performed the in vitro assays. Y.J., Z.L. and T.D. worked with the animal models and performed histochemical staining. Y.J., A.Z., X.W. and L.C. performed the statistical analysis, wrote and revised the manuscript. All the authors have read and approved the final manuscript. Funding This research was funded by the National Natural Science Foundation of China (82270953), the Shanghai Rising-Star Program (21QA1405400), and the Natural Science Foundation of Shanghai (22ZR1436400). Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate All the animal surgical experiments performed in this research were approved by the Animal Ethics Committee of Shanghai Ninth People’s Hospital affiliated with Shanghai Jiao Tong University School of Medicine (License No. SCXK (Shanghai) 2012-0007). Consent for publication All authors read and agreed to submit the manuscript. 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Supplementary Files SupportingInformation20240530.docx floatimage1.png Scheme 1 Preparation of bacteria targeting nanosystem Ce6@ZIF-8-PDA/UBI and its mechanism of combating bacteria and biofilms based on synergistic photodynamic and photothermal treatment. Cite Share Download PDF Status: Published Journal Publication published 23 Jan, 2025 Read the published version in Journal of Nanobiotechnology → Version 1 posted Editorial decision: Revision requested 25 Jun, 2024 Reviews received at journal 24 Jun, 2024 Reviews received at journal 24 Jun, 2024 Reviews received at journal 24 Jun, 2024 Reviews received at journal 23 Jun, 2024 Reviews received at journal 20 Jun, 2024 Reviewers agreed at journal 19 Jun, 2024 Reviewers agreed at journal 19 Jun, 2024 Reviews received at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 15 Jun, 2024 Reviewers agreed at journal 14 Jun, 2024 Reviewers agreed at journal 14 Jun, 2024 Reviewers invited by journal 14 Jun, 2024 Editor assigned by journal 08 Jun, 2024 Submission checks completed at journal 08 Jun, 2024 First submitted to journal 03 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4522338\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":317907031,\"identity\":\"9a1010a1-286e-48aa-95fd-32c4e4bd6aaf\",\"order_by\":0,\"name\":\"Wenxuan Shi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Case Western Reserve University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wenxuan\",\"middleName\":\"\",\"lastName\":\"Shi\",\"suffix\":\"\"},{\"id\":317907032,\"identity\":\"0f870dfc-10cf-4dff-b276-73330d729fe4\",\"order_by\":1,\"name\":\"Ao Zheng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ao\",\"middleName\":\"\",\"lastName\":\"Zheng\",\"suffix\":\"\"},{\"id\":317907033,\"identity\":\"e0a2754f-b445-47e6-9a71-b1f40d8ac10e\",\"order_by\":2,\"name\":\"Yu Jin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yu\",\"middleName\":\"\",\"lastName\":\"Jin\",\"suffix\":\"\"},{\"id\":317907034,\"identity\":\"6a6bc1ae-7e21-4e03-8844-1a639e19ac7d\",\"order_by\":3,\"name\":\"Zhuoyuan Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Clinical Research Center for Oral Diseases\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhuoyuan\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":317907035,\"identity\":\"a5bffb20-dbb3-4f6e-81f0-1367df0ab517\",\"order_by\":4,\"name\":\"Tanjun Deng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Clinical Research Center for Oral Diseases\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Tanjun\",\"middleName\":\"\",\"lastName\":\"Deng\",\"suffix\":\"\"},{\"id\":317907036,\"identity\":\"a98b1fe4-b964-4fc3-ac38-1f25b457f358\",\"order_by\":5,\"name\":\"Xiao Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xiao\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":317907037,\"identity\":\"b21c5037-e774-47d9-8db2-4b1b6cb7b0bc\",\"order_by\":6,\"name\":\"Lingyan Cao\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYDACdiB+YABiNDY+/ECUFmYgTgBp4TncbCxBvBYQQyK9TYCHGB38zTwGDAkFdxL7Zz5sY5BgsJPTbSCgReIwSIvBs8QZtxPbHhQwJBubHSCgxYAZrOVwYsPtxHYDCYYDiduI1jL/5sE2CR6StGy4wUikFonDbAUgLcYbzyQCA9mACL/wtzdvYPjw57DsvOPHHz78UGEnR1ALAwOH+Q8g6dgAcSdB5SDA/gBE2hOldhSMglEwCkYmAAD6tUHu7SqBqAAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Lingyan\",\"middleName\":\"\",\"lastName\":\"Cao\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-06-03 14:09:13\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4522338/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4522338/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12951-025-03126-2\",\"type\":\"published\",\"date\":\"2025-01-23T15:57:53+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":58916282,\"identity\":\"ff78c661-4303-49c5-b699-c50bcd6eec3e\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:54:40\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":4475831,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eCharacterization and photodynamic effects of nanoparticles. a) TEM image of ZIF-8 and ZIF-8-PDA. b) DLS\\u0026nbsp;particle size distribution.\\u0026nbsp;c) N\\u003c/strong\\u003e\\u003csub\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sub\\u003e\\u003cstrong\\u003e\\u0026nbsp;adsorption–desorption isotherms. d) ESR spectra of Ce6@ZIF-8-PDA/UBI nanoparticles treated with or without laser irradiation (808 nm, 5 min, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e) with 2,2,6,6-tetramethylpiperidine (TEMP) as a spin trap agent to capture \\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e1\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eO\\u003c/strong\\u003e\\u003csub\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sub\\u003e\\u003cstrong\\u003e. e-g) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eIn vitro\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e photodynamic effects of Ce6@ZIF-8-PDA/UBI nanoparticles. Chromogenic reaction of TMB under different e) power densities of laser irradiation (808 nm, 5 min, 200 μg/mL Ce6@ZIF-8-PDA/UBI), f) irradiation time (808 nm, 200 μg/mL Ce6@ZIF-8-PDA/UBI, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e), and g) Ce6@ZIF-8-PDA/UBI concentrations (808 nm, 5 min, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e).\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/da0deb81653d76e2ac46e5e5.png\"},{\"id\":58915750,\"identity\":\"9ff29bb9-d71e-419f-aa79-a011a1173233\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":3797158,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eNear-infrared photothermal performance. a) Digital thermal images and b) Temperature elevating curves of ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI nanoparticles (200 μg/mL) under laser irradiation (808 nm, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). c) Temperature elevating curves of Ce6@ZIF-8-PDA/UBI under different power densities of laser irradiation (808 nm). d) Temperature elevating curves of Ce6@ZIF-8-PDA/UBI with different concentrations under laser irradiation (808 nm, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). e, f) Heating and cooling curves of Ce6@ZIF-8-PDA/UBI under laser irradiation (808 nm, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). g) Linear fit of cooling time versus the negative natural logarithm of the driving force temperature.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/8610b6ba9e613811386e1b7f.png\"},{\"id\":58915759,\"identity\":\"ebe98244-247c-4f7b-b6fe-1ce9a7fddacf\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":39052474,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eAfter 2-h statical incubation with different particles, a) aggregation of \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e was observed by CLSM. b) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e targeting was also imaged by CLSM (scale bar: 1 μm) and SEM (scale bar: 400 nm).\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/957f8d2bfc637be9b671b425.png\"},{\"id\":58915756,\"identity\":\"1f1a40c3-3487-4ea7-ae01-fe203407a09e\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":12405341,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003ea, b) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e and c, d) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eE. coli\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e was respectively incubated with different nanoparticles without (NIR-) or with (NIR+) treatment of laser irradiation (808 nm, 5 min, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). a, c) Photographs of bacterial colonies and the corresponding antibacterial ratio statistics (*\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003ep\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e0.05 compared with other groups). Data are means±SD (n=3). b, d) Images in the upper two lines: live/dead fluorescent staining assays (green: all bacteria stained by SYTO9; red: dead bacteria stained by PI; yellow: merge. Scale bar: 10 μm). Images in the third line: SEM analysis (scale bar: 600 nm for \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus, \\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e800 nm for\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003e E. coli\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e). Images in the fourth line: TEM analysis (scale bar: 200 nm for \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus, \\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e800 nm for\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003e E. coli\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e). (Group I: ZIF-8; Group II: Ce6@ZIF-8; Group III: Ce6@ZIF-8-PDA; Group IV: Ce6@ZIF-8-PDA/UBI).\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/435a0e286ec72b1f73fd69b3.png\"},{\"id\":58916281,\"identity\":\"d28a4c71-ce33-4ab9-a5ec-0d3e6e63ddc3\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:54:40\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":7505040,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eAntibacterial activity of different nanoparticles against a) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eF. nucleatum\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e and b) \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eP. gingivalis\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e under laser irradiation (808 nm, 5 min, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). The corresponding antibacterial ratio statistics were calculated (n=3); *\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003ep\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e\\u0026lt;0.05 compared with other groups. c) 3D-CLSM images showing the penetration and accumulation of different nanoparticles in \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eP. gingivalis\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e biofilms (green: biofilm; red: particles. d, e) Confocal images of \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eP. gingivalis\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e biofilms without (NIR-) or with (NIR+) treatment of laser irradiation (808 nm, 5 min, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e) stained by SYTO 9 and PI. (Group I: ZIF-8; Group II: Ce6@ZIF-8; Group III: Ce6@ZIF-8-PDA; Group IV: Ce6@ZIF-8-PDA/UBI).\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage6.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/deb5416092d9956335f212a5.png\"},{\"id\":58915752,\"identity\":\"79e09538-2fac-480c-be62-ca564ee0fe81\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":6,\"title\":\"Figure 6\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":4794575,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eIn vivo\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e effect of nanoparticles on wound healing in an infected full-thickness skin defect model. a) Digital thermal images of \\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003eS. aureus\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e-infected mice treated with PBS and Ce6@ZIF-8-PDA/UBI nanoparticles under laser irradiation (808 nm, 1.3 W/cm\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e2\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003e). b) Representative images of the planktonic growth of bacteria in samples collected from the infected wound site after NIR irradiation treatment. c) Photographs of the different groups treated wounds at 1, 3, 7, and 14 days, and d) the corresponding simulation of the wound area. e) Quantitative analysis of the wound area of different groups. Data are means±SD (n=3); *\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003ep\\u003c/strong\\u003e\\u003c/em\\u003e\\u003cstrong\\u003e\\u0026lt;0.05 compared with other groups. f) Histological evaluations of the bacteria-infected skin tissues after different treatments on day 14, including HE staining (Upper) and Masson’s trichome staining (lower). (Group I: ZIF-8; Group II: Ce6@ZIF-8; Group III: Ce6@ZIF-8-PDA; Group IV: Ce6@ZIF-8-PDA/UBI).\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage7.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/862710df6a2686f8418c12c6.png\"},{\"id\":58916283,\"identity\":\"9079e46c-e34b-4b86-bda7-2bd56247c9c1\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:54:40\",\"extension\":\"png\",\"order_by\":7,\"title\":\"Figure 7\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":11901987,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eHistological evaluation of the antibacterial capacity of nanoparticles. Infection around implants treated with different nanoparticles (NIR+) assessed by HE staining.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage8.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/0ace55504eba350b3c1f2641.png\"},{\"id\":58915757,\"identity\":\"ce56d643-fda2-4cea-a28e-f711505bd5c4\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":8,\"title\":\"Figure 8\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":20088607,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eBiosafety evaluation of different nanoparticles. a) Viability of L929 cells treated with different concentrations of particles after 24h. *\\u003c/strong\\u003e\\u003cem\\u003e\\u003cstrong\\u003ep\\u003c/strong\\u003e\\u003c/em\\u003e \\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u003cstrong\\u003e0.05 compared with the denoted groups (n=3). b) Cytotoxicity of Ce6@ZIF-8-PDA/UBI by hemolysis test. c) HE staining images of major organs (including heart, kidney, spleen, liver, and lung) after treatment of different nanoparticles.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage9.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/a7dbe45057bc108cfb236ac8.png\"},{\"id\":58915754,\"identity\":\"b15cd805-fdc2-4d16-bbbc-54c5bf2afe9e\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":383875,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SupportingInformation20240530.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/8c3e29d638b713601b662fe0.docx\"},{\"id\":58915755,\"identity\":\"fca0ca97-3daf-40ac-b84b-1100b7fef132\",\"added_by\":\"auto\",\"created_at\":\"2024-06-24 05:46:40\",\"extension\":\"png\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":13174104,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eScheme 1 Preparation of bacteria targeting nanosystem Ce6@ZIF-8-PDA/UBI and its mechanism of combating bacteria and biofilms based on synergistic photodynamic and photothermal treatment.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4522338/v1/b4b1b54111baae37d9541823.png\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Photodynamic and photothermal bacteria targeting nanosystems for synergistically combating bacteria and biofilms\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eBacterial infections have been classified by the World Health Organization (WHO) as one of the leading causes of global mortality over the past 15 years [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. According to reports from the National Institutes of Health (NIH) in the United States, as many as 80% of bacterial infections are associated with biofilm formation [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Bacterial biofilms are dense bacterial communities encased in self-produced extracellular polymeric substances (EPSs) that can elude the host's adaptive and innate immune system. Biofilms are particularly concerning in chronic wounds, where they are prevalent in approximately 78.2% of cases, posing a significant hindrance to the healing process [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. Closed wounds with biofilm infections still show functional problems, such as a compromised extracellular matrix and impaired barriers, leading to recurring wound problems [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Biofilm formation also occurs in surgical procedures involving implants. Bacteria adhere to the implant during surgery, forming biofilms and causing infections. As these biofilms mature, they release bacteria, which spread widely and cause recurrent infections, ultimately leading to implant failure [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Notably, oral biofilms represent another highly complex challenge that can lead to chronic oral infections, including dental caries, periodontal diseases, peri-implantitis, and even systemic conditions affecting the gastrointestinal tract and cardiovascular system [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Treating these infections traditionally involves antibiotics, but biofilm-encased bacteria are highly resistant and require prolonged and high-dose antibiotic treatment, which can worsen resistance [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Current approaches to oral biofilm treatment involve periodic mechanical disruption and antimicrobial use, but they often require professional intervention and may not fully resolve secondary infections [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Therefore, there is an urgent need to explore innovative therapeutic strategies to control infections and eradicate biofilms.\\u003c/p\\u003e \\u003cp\\u003ePhotodynamic therapy (PDT) has recently gained recognition as an effective, noninvasive antimicrobial treatment [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Using photosensitizers, PDT generates reactive oxygen species (ROS) when exposed to light [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e], offering advantages such as resistance to drug resistance, painlessness, quick treatment, and minimal tissue damage [\\u003cspan additionalcitationids=\\\"CR12\\\" citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. Chlorin e6 (Ce6), derived from natural chlorophyll and an FDA-approved photosensitizer, has advantages such as efficient ROS generation, brief photosensitization, and strong red-light absorption [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. However, Ce6 faces challenges due to its limited water solubility and similar charge to bacteria. The development of an advanced antimicrobial PDT system for efficient photosensitizer release, improved penetration, and prolonged retention is crucial. Therefore, nanocarriers have been increasingly applied to assist in the penetration and transmembrane transport of hydrophobic photosensitizers in biofilms [\\u003cspan additionalcitationids=\\\"CR16 CR17 CR18 CR19\\\" citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. Zeolitic imidazolate framework (ZIF) is a promising nanocarrier with porosity, stability, and tunability [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. Simultaneously, the pH-sensitive degradation of ZIF-8 aligns perfectly with the acidic microenvironment inside bacterial biofilms, rendering it an ideal choice for controlled-release photosensitizer platforms such as Ce6 [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eDue to the limitations of photosensitizers, PDT sometimes requires a series of rational methods and strategies to work together to achieve better antimicrobial results. It has been reported that the combination of PDT and photothermal therapy (PTT) has an excellent therapeutic effect in treating bacterial infection [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. PTT uses photothermal conversion materials under the excitation of a specific light source to convert light energy into heat energy, resulting in excessive heat and leading to protein denaturation or cell membrane damage in bacteria and cells to achieve sterilization, which shows great potential in the treatment of drug-resistant bacteria and bacterial biofilms [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. Under the synergistic action of PDT and PTT, the bactericidal effects of Ce6 on \\u003cem\\u003eS. aureus\\u003c/em\\u003e were significantly enhanced [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. The dual-mode antibacterial conjugated nanoparticles had a photothermal effect and sensitized the cells to surrounding oxygen [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. Polydopamine (PDA) is an efficient organic photosensitizer with high biocompatibility and biodegradability. Due to its exceptional near-infrared (NIR) absorption and photothermal conversion efficiency, PDA might be an ideal candidate for antibacterial PTT. Moreover, PDA molecules with extensive functional groups, such as amine, catechol, and phenolic hydroxyl groups, can easily interact with other molecules, such as peptides, through functional groups via chemical bonds, electrostatic attraction, or π-π interactions. Similarly, PDA can rapidly form a conformal layer by being deposited on nanoparticle surfaces. PDA may also increase the adhesion of nanocarriers to bacteria to some extent [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]. Therefore, PDA can be used as a PTT coating on the nanocarrier surface and as a binder for further functional modification.\\u003c/p\\u003e \\u003cp\\u003eOne major challenge in combating biofilms is their robust self-defense mechanisms. Achieving effective biofilm penetration is crucial, but this can be challenging for nanoparticles, even though they can enter biofilm pores. To address this issue, we aimed to enhance nanoparticle performance by modifying them to better adhere to and target bacteria, thus improving antimicrobial penetration. We utilized antimicrobial peptides, such as ubiquicidine (UBI), specifically the UBI (29\\u0026ndash;41) peptide. It is a cationic peptide chain containing six positively charged amino acids and can selectively bind to bacterial cell membranes through electrostatic forces, particularly at infection sites [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. We hypothesized that modifying nanocarriers with UBI (29\\u0026ndash;41) could enhance bacterial targeting and biofilm penetration by promoting electrostatic interactions with bacterial membranes. To achieve this goal, we coated Ce6-loaded ZIF-8 nanoparticles with PDA/UBI to develop advanced antibacterial treatments for clinical use.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eThis study introduced a novel approach for a metal-organic framework (MOF)-based nanosystem, Ce6@ZIF-8-PDA/UBI, to effectively manage and eliminate biofilm-related infections. We synthesized these nanoparticles using PDA chemistry and grafted UBI to provide more anchors for bacteria and deep penetration into biofilms. We investigated the antibacterial properties of Ce6@ZIF-8-PDA/UBI under NIR irradiation, which significantly improved its activity against \\u003cem\\u003eS. aureus, E. coli, F. nucleatum, and P. gingivalis\\u003c/em\\u003e compared to that of their counterparts. It also exhibited exceptional light-driven antibiofilm activity against \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e oral biofilms. This was due to efficient bacterial adhesion mediated by PDA/UBI modifications and synergistic PDT/PTT facilitated by Ce6/PDA interactions. Moreover, we assessed the \\u003cem\\u003ein vivo\\u003c/em\\u003e effects of the nanosystem on infected wound healing and peri-implant infection control. The Ce6@ZIF-8-PDA/UBI nanosystem, with synergistic PTT and PDT, offers a promising approach for treating bacterial infections and biofilms (Scheme \\u003cspan refid=\\\"Sch1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\"},{\"header\":\"Materials and methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSynthesis of Ce6@ZIF-8-PDA/UBI\\u003c/h2\\u003e \\u003cp\\u003eSynthesis of Ce6@ZIF-8: 180 mg of 2-methylimidazole (HMIM) and 20 mg of Zn(NO\\u003csub\\u003e3\\u003c/sub\\u003e)\\u003csub\\u003e2\\u003c/sub\\u003e\\u0026middot;6H\\u003csub\\u003e2\\u003c/sub\\u003eO were dispersed separately in 1 mL of methanol. A solution of 0.5 mL of Ce6 (1.0 mg/mL in dimethyl sulfoxide) and HMIM (180 mg/mL in methanol) was mixed and stirred for 5 minutes. Then, Zn(NO\\u003csub\\u003e3\\u003c/sub\\u003e)\\u003csub\\u003e2\\u003c/sub\\u003e\\u0026middot;6H\\u003csub\\u003e2\\u003c/sub\\u003eO (20 mg/mL in methanol) was swiftly added. The obtained solution was stirred at room temperature in the dark for 1.5 hours. Upon completion, the collected Ce6@ZIF-8 was centrifuged and washed, followed by resuspension and storage in the dark at 4\\u0026deg;C. Control samples of ZIF-8 nanoparticles were synthesized similarly. To quantify unembedded Ce6, the supernatant was collected and analyzed using a microplate reader (Spark 10M, TECAN, Switzerland) to obtain the OD values. The Ce6 loading efficiency (LE) was then calculated as (Total Ce6 amount-unembedded Ce6 amount)/Ce6@ZIF-8 weight\\u0026times;100%.\\u003c/p\\u003e \\u003cp\\u003eSynthesis of Ce6@ZIF-8-PDA: Initially, a dopamine solution (3.2 mL, 25 mM in methanol) was introduced to a Ce6@ZIF-8 solution in methanol (32 mL). The resulting mixture was refluxed at 60 ℃ for 7 hours. Next, the resulting Ce6@ZIF-8-PDA was subjected to a washing and resuspension process.\\u003c/p\\u003e \\u003cp\\u003eSynthesis of Ce6@ZIF-8-PDA/UBI: Next, 400 \\u0026micro;L of UBI solution (8 mg/mL) was added at ambient temperature for 1 hour. After necessary washing and overnight freeze-drying, Ce6@ZIF-8-PDA/UBI was obtained. The calculation of Ce6 loading efficiency was based on the following formula: (Corresponding Ce6@ZIF-8 weight\\u0026times;LE\\u003csub\\u003eCe6@ZIF-8\\u003c/sub\\u003e)/Ce6@ZIF-8-PDA/UBI weight\\u0026times;100%. To investigate whether UBI was grafted on the final nanoparticles, Cy5.5-labeled UBI was used, and fluorescence images were acquired via confocal laser scanning microscopy (CLSM, TCS SP8).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCharacterization of Ce6@ZIF-8-PDA/UBI\\u003c/h2\\u003e \\u003cp\\u003eThe morphologies of the nanoparticles were examined by transmission electron microscopy (TEM, HT-7800, Hitachi, Japan). For dynamic light scattering (DLS) measurements, a Malvern Zetasizer Nanoseries (Nano ZS90, Nano-ZS 90, Malvern Instrument, United Kingdom) was used. Fourier transform infrared (FT-IR) spectroscopy was performed using a Nicolet 550 spectrophotometer. X-ray diffraction (XRD) analysis was conducted using a Bruker D8 Advance X-ray diffractometer (Bruker AXS, Germany). A surface area and porosity analyzer (Micromeritics Tristar 3020, USA) was utilized to assess the nitrogen adsorption-desorption properties.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eAnalysis of ROS generation\\u003c/h2\\u003e \\u003cp\\u003eTo evaluate ROS generation, we employed an electron spin resonance (ESR) spectrometer (JEOL-FA200, Japan) to record ESR spectra. This assessment involved treatments with or without laser irradiation (808 nm, 5 minutes, 1.3 W/cm\\u0026sup2;) in the presence of 2,2,6,6-tetramethylpiperidine (TEMP) as a spin trap agent to capture ROS. Moreover, we used 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic indicator to analyze ROS generation in Ce6@ZIF-8-PDA/UBI nanoparticles upon 808 nm laser irradiation. Briefly, a solution consisting of 4 mM TMB and 100 \\u0026micro;g/mL Ce6@ZIF-8-PDA/UBI was subjected to irradiation using an 808 nm laser at various power densities (0, 0.6, 1.3, and 2.0 W/cm\\u0026sup2;) for 5 minutes. Alternatively, the same solution was exposed to the laser for varying durations (0, 1, 3, 5, 7, and 9 minutes) while maintaining a constant power density of 1.3 W/cm\\u0026sup2;. Furthermore, we investigated the photothermal characteristics of Ce6@ZIF-8-PDA/UBI solutions in PBS at different concentrations (0, 100, 200, 300, 400, and 500 \\u0026micro;g/mL) under NIR irradiation (5 minutes, 808 nm, 1.3 W/cm\\u0026sup2;). After irradiation, 100 \\u0026micro;L of each solution above was dispensed into a 96-well microplate and subsequently analyzed using a microplate reader (Spark 10M, TECAN, Switzerland) following photograph recording.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eNIR photothermal performance\\u003c/h2\\u003e \\u003cp\\u003eThe photothermal properties of the prepared nanosystems were evaluated by using an infrared thermal camera (Fotric 226S, Fotric Inc., China). Real-time temperature monitoring and thermal imaging were conducted to obtain detailed temperature elevation profiles for various nanoparticle compositions, including ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI (all at 200 \\u0026micro;g/mL). These measurements were taken under controlled laser irradiation conditions at 808 nm with a power density of 1.3 W/cm\\u0026sup2;. Furthermore, temperature elevation profiles of Ce6@ZIF-8-PDA/UBI nanoparticles (200 \\u0026micro;g/mL) under various power densities (0, 0.6, 1.3, and 2.0 W/cm\\u0026sup2;) of 808 nm laser irradiation were also recorded. Likewise, different concentrations (100, 200 and 400 \\u0026micro;g/mL) of Ce6@ZIF-8-PDA/UBI aqueous solutions were systematically studied under constant laser irradiation conditions (808 nm, 1.3 W/cm\\u0026sup2;). Additionally, a comprehensive assessment of the thermal properties of Ce6@ZIF-8-PDA/UBI nanoparticles in PBS (200 \\u0026micro;g/mL) was performed. The solution underwent successive cycles of 5 minutes of laser irradiation (808 nm, 1.3 W/cm\\u0026sup2;) followed by natural cooling to 28.7\\u0026deg;C. The photothermal conversion efficiency of the Ce6@ZIF-8-PDA/UBI nanoparticles was calculated using the following equation according to a previous study [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e].\\u003cdiv id=\\\"Equa\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equa\\\" name=\\\"EquationSource\\\"\\u003e\\n$$\\\\eta =\\\\frac{hS({T}_{max}-{T}_{suur})}{\\\\text{I}(1-{10}^{-{A}_{808}})}$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003cp\\u003ewhere \\u003cem\\u003eT\\u003c/em\\u003e\\u003csub\\u003e\\u003cem\\u003emax\\u003c/em\\u003e\\u003c/sub\\u003e is the maximum temperature of the Ce6@ZIF-8-PDA/UBI solution, \\u003cem\\u003eTsuur\\u003c/em\\u003e is the ambient temperature, and \\u003cem\\u003eA\\u003c/em\\u003e is the absorbance of the Ce6@ZIF-8-PDA/UBI solution at 808 nm (A\\u003csub\\u003e808\\u003c/sub\\u003e\\u0026thinsp;=\\u0026thinsp;0.1522). The \\u003cem\\u003ehS\\u003c/em\\u003e was calculated using the following equation:\\u003cdiv id=\\\"Equb\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equb\\\" name=\\\"EquationSource\\\"\\u003e\\n$$hS=-\\\\frac{{\\\\sum }_{i}{m}_{i}{\\\\text{C}}_{i}}{{\\\\tau }_{s}}$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003cp\\u003ewhere \\u003cem\\u003em\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.3 g, \\u003cem\\u003ec\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;4.2 J/g, and τs is the slope of the fitting line between cooling time \\u003cem\\u003et\\u003c/em\\u003e and -ln\\u003cem\\u003eθ\\u003c/em\\u003e:\\u003cdiv id=\\\"Equc\\\" class=\\\"Equation\\\"\\u003e\\u003cdiv format=\\\"TEX\\\" class=\\\"mathdisplay\\\" id=\\\"FileID_Equc\\\" name=\\\"EquationSource\\\"\\u003e\\n$$\\\\theta =\\\\frac{T-{T}_{suur}}{{T}_{max}-{T}_{suur}}({\\\\tau }_{s}=139.1)$$\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eSynergistic antibacterial activity of PTT and PDT\\u003c/b\\u003e \\u003cb\\u003ein vitro\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBacterial aggregation and targeting\\u003c/h2\\u003e \\u003cp\\u003eFirst, \\u003cem\\u003eS. aureus\\u003c/em\\u003e was cultured overnight in LB at 37\\u0026deg;C. The culture was then concentrated at 5000 rpm for 5 minutes and transferred to PBS. Subsequently, the bacterial mixture was kept stationary and exposed to Cy5.5-labeled ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles. The plates were incubated at 37 ℃ for 2 hours. The bacteria were then concentrated and subjected to three washes with PBS before being stained with SYTO9 dye. The resultant aggregated bacterial samples were observed using CLSM (TCS SP8, Leica, Germany). To investigate bacterial targeting and substantiate the binding between nanoparticles and bacteria, the samples were diluted, resuspended, and analyzed using CLSM and scanning electron microscopy (SEM, Hitachi, S4800).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePlate counting\\u003c/h2\\u003e \\u003cp\\u003eCoculturing involved a 1 mL aliquot of bacterial suspensions (\\u003cem\\u003eS. aureus, E. coli\\u003c/em\\u003e, 2\\u0026times;10\\u003csup\\u003e8\\u003c/sup\\u003e colony-forming units (CFU)/mL) in PBS buffer (0.01 M, pH 7.4) supplemented with 1 mL of various nanoparticles (ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI) at 37\\u0026deg;C for 2 hours. The bacteria in the NIR\\u0026thinsp;+\\u0026thinsp;groups were irradiated with an 808 nm laser (1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e) for 5 minutes, while those in the NIR- groups remained untreated. After coculturing, all bacteria were diluted and cultured on LB plates for 18 hours at 37\\u0026deg;C. The antibacterial efficacy of each group was evaluated by photographing and quantifying the CFUs. Oral bacteria, including \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e, were also investigated similarly.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLive/dead bacterial fluorescence assays\\u003c/h2\\u003e \\u003cp\\u003eAfter applying different samples to the bacterial suspension, following centrifugation and washing with PBS, a mixture of propidium iodide (PI) and SYTO9 dye (1 \\u0026micro;L) (Invitrogen Detection Technologies, USA) was added. This blend was subsequently incubated in darkness at room temperature for 15 minutes. Due to the different integrity of the bacterial cell membranes, all bacteria could be labeled with green fluorescence by SYTO9. In contrast, only dead bacteria could be marked explicitly with red fluorescence by PI. Finally, CLSM (Leica TCS SP8) was used for cell imaging.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSEM and TEM imaging\\u003c/h2\\u003e \\u003cp\\u003eNext, the bacterial suspensions containing \\u003cem\\u003eS. aureus\\u003c/em\\u003e and \\u003cem\\u003eE. coli\\u003c/em\\u003e were centrifuged and fixed, and the bacterial morphology was examined and visualized via SEM imaging (S4800, Hitachi, Japan) and TEM imaging (HT-7800, Hitachi, Japan).\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eSynergistic antibiofilm activities of PTT and PDT\\u003c/b\\u003e \\u003cb\\u003ein vitro\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBiofilm penetration\\u003c/h2\\u003e \\u003cp\\u003e \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e was cultured overnight in BHI medium at 37\\u0026deg;C, followed by dilution with the medium. The bacterial suspension was placed in a 6-well plate containing sterile coverslips (18 \\u0026times; 18 mm). The coverslips were vertically positioned and subjected to static cultivation at 37\\u0026deg;C for 48 hours. After the formation of mature biofilms on the coverslips, the media were removed, and the biofilms were washed three times with sterile PBS buffer to isolate the planktonic bacteria effectively. The biofilms were then exposed to distinct Cy5.5-labeled particles in suspension (200 \\u0026micro;g/mL) for 2 hours, during which they were gently agitated (50 rpm). After this exposure period, the biofilms were rinsed with PBS to eliminate any free particles. Subsequently, the biofilms were stained with FITC-labeled concanavalin A (FITC-ConA) and finally subjected to CLSM imaging.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBiofilm survival\\u003c/h2\\u003e \\u003cp\\u003eIn the biofilm survival assay, the biofilms were subsequently exposed to various particles in suspension (200 \\u0026micro;g/mL). Following a 2-hour coculturing period with gentle agitation (50 rpm) at 37 ℃, the biofilms in the light irradiation groups were exposed to an 808 nm laser (1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e) for 5 minutes. After this irradiation, the biofilms were washed with PBS to eliminate any free particles and then subjected to staining with PI and SYTO9 dye following the manufacturer's instructions. Finally, the biofilms were imaged using CLSM.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eIn vivo\\u003c/b\\u003e \\u003cb\\u003einfection control and the infected tissue repair\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003eTo confirm the \\u003cem\\u003ein vivo\\u003c/em\\u003e antibacterial effect of the synthesized nanosystems, a mouse cutaneous wound infection model and a rat femur peri-implantitis model were selected. All the animal surgical experiments performed in this research were approved by the Animal Ethics Committee of Shanghai Ninth People\\u0026rsquo;s Hospital affiliated with Shanghai Jiao Tong University School of Medicine.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eMouse cutaneous wound infection model\\u003c/h2\\u003e \\u003cp\\u003eA full-thickness skin defect model with \\u003cem\\u003eS. aureus\\u003c/em\\u003e infection was established using 8-week-old Kunming mice. Initially, a sterile scalpel was utilized to create a skin defect measuring approximately 10 mm in diameter. Subsequently, 100 \\u0026micro;L of \\u003cem\\u003eS. aureus\\u003c/em\\u003e solution (1\\u0026times;10\\u003csup\\u003e8\\u003c/sup\\u003e CFU/mL) in LB was introduced into the wound. Following a 24-hour postinfection period, the animals were randomly assigned to four groups (3 per group). Subsequently, 200 \\u0026micro;L of aqueous solution containing 200 \\u0026micro;g/mL ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, or Ce6@ZIF-8-PDA/UBI was individually applied to the wound site. On both days 1 and 3 within each group, the infected wound sites of the animals underwent irradiation with an 808 nm NIR laser (1.3 W/cm\\u0026sup2;, 5 minutes). On the third day, samples were collected from the wound site and treated with bacteria incubation for 24 h at 37\\u0026deg;C. Afterward, the bacterial suspensions were collected, and the OD600 was determined by using a microplate reader (Spark 10M, TECAN, Switzerland). On the 14th day, skin tissue encompassing the wound area was collected for subsequent histological analysis, including hematoxylin and eosin (HE) staining and Masson's trichrome staining. Within 14 days postsurgery, the macroscopic appearance and dimensions of the infected wound were documented at different time points through digital photography, employing a ruler for reference. On the 14th day, skin tissue encompassing the wound area was collected for subsequent histological analysis, including HE staining and Masson's trichrome staining.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eIn vivo peri-implant infection model\\u003c/h2\\u003e \\u003cp\\u003eTo further validate the effectiveness of the modified nanoparticles against peri-implant infection, a rat femur peri-implantitis model was established. The distinct titanium implants were immersed in a solution of inoculated \\u003cem\\u003eS. aureus\\u003c/em\\u003e bacteria (2\\u0026times;10\\u003csup\\u003e3\\u003c/sup\\u003e CFUs) to cultivate bacterial biofilms adhering to the implant surface. These implants were subsequently placed in suspensions of various modified nanoparticles for 2 hours. Prior to the procedure, male SD rats (8 weeks old) were anesthetized. The femur near the knee joint was exposed through an incision, and a narrow channel was created at the femoral condyle using a surgical drill. The animals were randomly categorized into the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI groups, and each animal received an implant featuring nanoparticle modifications. The subsequent steps involved careful suturing of the skin and soft tissue. On both days 1 and 3 within each group, each infected wounds underwent irradiation with an 808 nm NIR laser (1.3 W/cm\\u0026sup2;, 5 minutes). After 14 days of implantation, tissues surrounding the infected implant site were extracted for HE staining. This evaluation aimed to gauge the \\u003cem\\u003ein vivo\\u003c/em\\u003e antibiofilm efficacy of different nanoparticles. Additionally, major organs were collected and subjected to HE staining to assess potential \\u003cem\\u003ein vivo\\u003c/em\\u003e toxicity linked to the nanoparticles employed in the study.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec15\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eCCK-8 viability assay\\u003c/h2\\u003e \\u003cp\\u003eThe cell viability assessment of the prepared nanoparticles was conducted through a CCK-8 viability assay. L929 cells were seeded within 96-well plates at a density of 1\\u0026times;10\\u003csup\\u003e4\\u003c/sup\\u003e cells/well and allowed to adhere overnight at 37\\u0026deg;C in an atmosphere of 5% CO\\u003csub\\u003e2\\u003c/sub\\u003e and 95% air. Subsequently, the cells were exposed to the prepared ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles at various concentrations (0, 10, 50, 100, 200, 300, 400 and 500 \\u0026micro;g/mL) for 24 hours. Following this incubation, each well was supplemented with 10 \\u0026micro;L of CCK8 reagent (BestBio, Shanghai, China) and then incubated in the dark at 37\\u0026deg;C for 1.5 hours. The optical density of each well was subsequently assessed at 450 nm using a microplate reader (Spark 10M, TECAN, Switzerland).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec16\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eHemolytic assay\\u003c/h2\\u003e \\u003cp\\u003eVarious concentrations of Ce6@ZIF-8-PDA/UBI solutions (0.8 mL in PBS) were mixed with 0.2 mL of the collected PBS-diluted RBCs. The mixture was then cultured at room temperature for 4 hours. Afterward, the supernatant was collected through centrifugation, and the absorbance at 545 nm was measured using a microplate reader (Spark 10M, TECAN, Switzerland). Finally, the hemolysis ratio was calculated using the following equation:\\u003c/p\\u003e \\u003cp\\u003eHemolysis (%) = (OD\\u003csub\\u003eCe6@ZIF-8-PDA/UBI\\u003c/sub\\u003e-OD\\u003csub\\u003ePBS\\u003c/sub\\u003e)/(OD\\u003csub\\u003eddwater\\u003c/sub\\u003e-OD\\u003csub\\u003ePBS\\u003c/sub\\u003e) \\u0026times; 100%.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec17\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eAll data points were expressed as the mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD). The t-test and one-way analysis of variance (ANOVA) were used to compare values among groups. A \\u003cem\\u003ep\\u003c/em\\u003e value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered to indicate statistical significance. All the data analysis were conducted with SPSS Statistics 24 software.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec19\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSynthesis and characterization of nanoparticles\\u003c/h2\\u003e \\u003cp\\u003eThe microstructures of ZIF-8 and ZIF-8-PDA were assessed via TEM, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ea. The ZIF-8-PDA nanoparticles retained the original polyhedral shape of the ZIF-8 nanoparticles and displayed an approximate size of 100 nm. An obvious dark black layer could be found on the surface of the ZIF-8-PDA nanoparticles, which might be attributed to the PDA surface modification. Ce6@ZIF-8-PDA/UBI has a morphology similar to that of ZIF-8-PDA (Fig. \\u003cspan refid=\\\"MOESM1\\\" class=\\\"InternalRef\\\"\\u003eS1\\u003c/span\\u003e). The FT-IR spectra of ZIF-8-PDA confirmed the presence of a PDA shell, where the stretches at 1486 cm\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e and 1260 cm\\u003csup\\u003e\\u0026minus;\\u0026thinsp;1\\u003c/sup\\u003e correspond to the phenolic N-H and C-O of PDA, respectively (Fig. S2). DLS analysis (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eb) revealed that the size of the ZIF-8-PDA nanoparticles (93.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.6 nm) was slightly greater than that of the ZIF-8 nanoparticles (90.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.9 nm). A comparison of the XRD patterns of different nanoparticles (Fig. S3) implied that the introduction of PDA, Ce6, and UBI preserved the crystal structure of the ZIF-8 nanoparticles. The introduction of PDA, Ce6, and UBI led to a significant reduction in the intensity of the diffraction peaks. This attenuation was attributed to the external shielding effects of PDA and UBI and the internal placeholder effect of Ce6. The characteristic nitrogen adsorption-desorption isotherms for ZIF-8, ZIF-8-PDA, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI confirmed the porous properties of the particles (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ec). All samples displayed a type I isotherm, with a steepness in the low-pressure range (P/P\\u003csub\\u003e0\\u003c/sub\\u003e\\u0026thinsp;=\\u0026thinsp;0 to 0.1) indicating the presence of micropores. In contrast to those of ZIF-8, the isotherms of Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI showed reduced N\\u003csub\\u003e2\\u003c/sub\\u003e adsorption. This substantiated the successful modification of the ZIF-8 surface and Ce6 loading within the micropores. The Ce6 loading efficiency of Ce6@ZIF-8-PDA/UBI reached 47.86%\\u0026plusmn;2.68%. According to the fluorescence images (Fig. S4), the red signal of Cy5.5-labeled UBI could be verified in the Ce6@ZIF-8-PDA/UBI groups, which confirmed the successful grafting of UBI onto the nanoparticles.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec20\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eROS generation capacity\\u003c/h2\\u003e \\u003cp\\u003eBy employing ESR spectroscopy to identify the irradiation product of Ce6@ZIF-8-PDA/UBI triggered by NIR, TEMP was employed as a trapping probe for ROS. The spectral data in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ed show the NIR-induced generation of highly reactive singlet oxygen (\\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e) from Ce6@ZIF-8-PDA/UBI. A characteristic three-line spectrum of TEMP/\\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e with a balanced intensity of 1:1:1 was obtained. Conversely, Ce6@ZIF-8-PDA/UBI without NIR irradiation exhibited nearly no TEMP/\\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e signals under the same conditions. When subjected to NIR irradiation, the ROS generation capacity of the Ce6@ZIF-8-PDA/UBI nanoparticles was assessed using a TMB chromogenic reaction (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ee-g). The TMB solution underwent oxidation by \\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e produced by Ce6@ZIF-8-PDA/UBI nanoparticles under NIR irradiation, transitioning from colorless to blue, with two distinct absorption peaks emerging at 370 and 650 nm. The evaluation of \\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e production was investigated under different conditions including various concentrations (0, 100, 200, 300, 400, and 500 \\u0026micro;g/mL) of Ce6@ZIF-8-PDA/UBI nanoparticles, different power densities of 808 nm laser irradiation (0, 0.6, 1.3, and 2.0 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e), and various durations (0, 1, 3, 5, 7, and 9 min). Initial analysis revealed a distinct reliance of NIR-triggered \\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e production by Ce6@ZIF-8-PDA/UBI on the irradiation power density. The color deepening in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ee accompanied the increase in power density, and the absorption peak displayed a corresponding trend. Without NIR irradiation, negligible \\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e formation was observed. Furthermore, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ef-g, \\u003csup\\u003e1\\u003c/sup\\u003eO\\u003csub\\u003e2\\u003c/sub\\u003e production by Ce6@ZIF-8-PDA/UBI exhibited a positive correlation with irradiation time and nanoparticle concentration.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec21\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eNIR photothermal capacity\\u003c/h2\\u003e \\u003cp\\u003eAs shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ea and b, the temperature variations of the Ce6@ZIF-8-PDA solution and Ce6@ZIF-8-PDA/UBI solution upon 808 nm light irradiation increased over time. In contrast, the PBS, ZIF-8, and Ce6@ZIF-8 solutions did not significantly increase the temperature. Notably, the Ce6@ZIF-8-PDA solution reached 48.4 ℃ after 5 minutes of irradiation at 1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e. Similarly, the temperature of the Ce6@ZIF-8-PDA/UBI solution reached 47.2 ℃, indicating that the addition of UBI had minimal impact on the photothermal effect of Ce6@ZIF-8-PDA. The thermal performance test (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ec and d) revealed that at a nanoparticle concentration of 200 \\u0026micro;g/mL and an irradiation power of 1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e, the temperature of the Ce6@ZIF-8-PDA/UBI solution increased from 23.0 ℃ to 47.2 ℃ within 5 minutes. As the irradiation power increased from 0.6 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e to 1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e, the final solution temperature increased by approximately 8.7\\u0026deg;C. However, when the power was further increased to 2 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e, the temperature further increased by 8.9\\u0026deg;C. Notably, with an elevated nanoparticle concentration of 400 \\u0026micro;g/mL and a power of 1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e, the temperature of the particle solution increased to 50.7 ℃ after 5 minutes of irradiation. Subsequently, the photothermal stability of the Ce6@ZIF-8-PDA/UBI nanoparticles was evaluated through a comprehensive photothermal performance cycle. As exemplified in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ee, the temperature profiles exhibited remarkable resilience after five cycles of alternating laser activation and deactivation. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003ef and g, the calculated photothermal conversion efficiency for Ce6@ZIF-8-PDA/UBI was 22.43%.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eIn vitro\\u003c/b\\u003e \\u003cb\\u003eantibacterial effect of synergistic PDT/PTT activities\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003eTo evaluate the influence of nanoparticles on bacterial binding and aggregation, \\u003cem\\u003eS. aureus\\u003c/em\\u003e was incubated with Cy5.5-labeled nanoparticles, including ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003ea, a discernible aggregation of \\u003cem\\u003eS. aureus\\u003c/em\\u003e, denoted by the green fluorescence of SYTO9 dye, occurred upon exposure to nanoparticles featuring a PDA coating, including Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI nanoparticles. This outcome was attributed to the multivalent interactions between the nanoparticles and \\u003cem\\u003eS. aureus\\u003c/em\\u003e cell walls facilitated by the presence of the PDA layer. Notably, the introduction of UBI further potentiated bacterial aggregation, surpassing the effect of PDA alone. Upon dilution and resuspension, CLSM visualization (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eb) of \\u003cem\\u003eS. aureus\\u003c/em\\u003e treated with Ce6@ZIF-8-PDA/UBI nanoparticles revealed that the presence of green fluorescent clusters closely correlated with the distribution of red fluorescent dots along the surface and edges of the particles, resulting in overlapping areas exhibiting yellow fluorescence. Virtually all green fluorescently labeled bacteria exhibited dense red fluorescent material enveloping them. In contrast, the ZIF-8- and Ce6@ZIF-8-treated bacteria showed nearly no red particle adhesion. In the SEM images, adhered nanoparticles could also be clearly found on the surface of the bacteria in the Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI groups. Ce6@ZIF-8-PDA/UBI showed more aggregation on \\u003cem\\u003eS. aureus\\u003c/em\\u003e than did Ce6@ZIF-8-PDA.\\u003c/p\\u003e \\u003cp\\u003eFigure \\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003ea and c illustrates the CFU counts of \\u003cem\\u003eS. aureus\\u003c/em\\u003e and \\u003cem\\u003eE. coli\\u003c/em\\u003e after incubation with different nanoparticles. There were no significant discrepancies in CFU counts without NIR irradiation. In contrast, upon NIR exposure, substantial reductions in CFU counts were evident for \\u003cem\\u003eS. aureus\\u003c/em\\u003e and \\u003cem\\u003eE. coli\\u003c/em\\u003e treated with Ce6@ZIF-8-PDA (Group III) and Ce6@ZIF-8-PDA/UBI (Group IV), with the latter exhibiting more potent antibacterial effects. To further validate the \\u003cem\\u003ein vitro\\u003c/em\\u003e antibacterial efficacy of the NIR-activated nanoplatforms against \\u003cem\\u003eS. aureus\\u003c/em\\u003e and \\u003cem\\u003eE. coli\\u003c/em\\u003e, live/dead fluorescence staining assays were employed. Consistent with the results of the plate counting experiments, the absence of NIR treatment resulted in predominantly green-stained bacteria, indicating their viability (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eb and d). Conversely, NIR-treated Ce6@ZIF-8 (Group II), Ce6@ZIF-8-PDA (Group III), and Ce6@ZIF-8-PDA/UBI (Group IV) displayed a progressive increase in yellow signals resulting from the overlap of green and red fluorescence. This trend indicated heightened antibacterial activity, most prominently observed in the NIR-activated Ce6@ZIF-8-PDA/UBI group. Subsequently, the antibacterial impact of the distinct nanoparticles was qualitatively assessed through SEM and TEM analysis. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eb and d, the bacterial skeleton structures within the Ce6@ZIF-8-PDA/UBI group appeared dispersed and collapsed, accompanied by bacterial surface wrinkling, distortion, and even complete dissolution.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eIn vitro\\u003c/b\\u003e \\u003cb\\u003esynergistic PDT/PTT activities against oral bacteria and oral biofilms\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003eThe antibacterial activity of the distinct biomaterials against \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e was further investigated using the standard plate counting method. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ea and b, no significant reductions were observed across the various groups without NIR treatment. Notably, the most pronounced antibacterial effect was evident in the Ce6@ZIF-8-PDA/UBI group (Group IV) after NIR treatment, highlighting the efficient antibacterial property of the particle system. The bacterial survival rate for different nanoparticles without irradiation (NIR- groups) remained at nearly 100%. However, upon irradiation (NIR\\u0026thinsp;+\\u0026thinsp;groups), the bacterial survival rate in the Ce6@ZIF-8 group (Group II) significantly decreased compared to that in the ZIF-8 group (Group I). Specifically, the bacterial survival rates after Ce6@ZIF-8 treatment reached 71.1%\\u0026plusmn;0.9% and 73.0%\\u0026plusmn;2.0% for \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e, respectively. This finding suggested that Ce6@ZIF-8-based PDT and PTT exhibited a moderate antibacterial effect on planktonic bacteria but could not eliminate bacteria at the safe concentrations utilized. However, the combination of PDA coating and Ce6 loading (Group III: Ce6@ZIF-8-PDA) led to a more substantial reduction in the bacterial count, nearly 70%, for both \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e. This finding underscores the exceptional \\u003cem\\u003ein vitro\\u003c/em\\u003e antibacterial activity arising from the synergistic action between Ce6 loading and the PDA layer within the nanosystem. Furthermore, the Ce6@ZIF-8-PDA system modified with UBI (Group IV: Ce6@ZIF-8-PDA/UBI) nearly eradicated all bacteria, including both \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e. In conclusion, the Ce6@ZIF-8-PDA/UBI nanoplatforms exhibited remarkable antibacterial activity through combined PDT and PTT.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe exploration of nanoparticle penetration within biofilms involved examining formed \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e biofilms stained with FITC-ConA. These biofilms were subsequently exposed to suspensions containing Cy5.5-labeled ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoplatforms, followed by comprehensive imaging through CLSM 3D visualization (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ec). Remarkably, the inclusion of PDA and UBI led to the most profound penetration by Cy5.5-labeled Ce6@ZIF-8-PDA/UBI within the biofilms, surpassing all other groups. This was evidenced by the uniform and vibrant distribution of red fluorescence arising from particles throughout the biofilm, extending even to its bottom layers. In stark contrast, the extent of Ce6@ZIF-8 penetration within the biofilm markedly decreased, signifying restricted penetration due to the absence of PDA, which hindered the adhesion and penetration of Ce6@ZIF-8 into the biofilm. The incorporation of PDA and UBI on the surface coating significantly enhanced the adhesion and targeting capabilities of the nanoplatform to the biofilm matrix. Consequently, this enhancement facilitated substantial penetration into the biofilm structure, leading to the accumulation of noticeable concentrations of Cy5.5-labeled nanoplatforms [\\u003cspan additionalcitationids=\\\"CR30\\\" citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eFor a comprehensive evaluation of the antibiofilm capabilities of the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoplatforms under various conditions (including with or without NIR treatment, 808 nm, 5 min, 1.3 W/cm\\u003csup\\u003e2\\u003c/sup\\u003e), a dual-staining approach involving PI and SYTO9 dye was employed. This approach allowed for the simultaneous visualization of live and dead cells within biofilms. The results were captured and analyzed using CLSM 3D imaging (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ed and e). Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ed shows biofilms in their intact state without NIR irradiation across all groups, exhibiting intense green fluorescence. In contrast, Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ee illustrates a shift in the response, with the NIR-irradiated ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI groups displaying decreased green fluorescence and increased red fluorescence. Notably, the NIR-activated Ce6@ZIF-8-PDA/UBI group exhibited the most prominent bactericidal effect on \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e biofilms. Collectively, these comprehensive findings underscore the robust antibacterial properties of Ce6@ZIF-8-PDA/UBI nanoparticles, especially when harnessed by NIR activation. These findings emphasize the potential of these nanoparticles for future applications in combating bacterial infections. The exceptional light-driven antibiofilm activity of Ce6@ZIF-8-PDA/UBI is likely a result of the efficient bacterial localization mediated by PDA/UBI and the PDT/PTT facilitated by Ce6/PDA interactions.\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eIn vivo\\u003c/b\\u003e \\u003cb\\u003estudy\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec22\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eTreatment of S. aureus infected skin wound healing\\u003c/h2\\u003e \\u003cp\\u003eWith the promising \\u003cem\\u003ein vitro\\u003c/em\\u003e antibacterial outcomes established, an investigation into the \\u003cem\\u003ein vivo\\u003c/em\\u003e antibacterial efficacy of different nanoparticles was carried out on a full-thickness skin defect model with \\u003cem\\u003eS. aureus\\u003c/em\\u003e infection. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ea, temperature fluctuations around the wound site during NIR light irradiation in the presence of Ce6@ZIF-8-PDA/UBI were apparent. A mere 5-minute session of NIR irradiation caused the wounds treated with Ce6@ZIF-8-PDA/UBI to experience a swift temperature increase from 32.0 to 47.9\\u0026deg;C. This rapid increase underlines the pronounced \\u003cem\\u003ein vivo\\u003c/em\\u003e PDT effect of Ce6@ZIF-8-PDA/UBI, showing its precise localization at the wound site. In contrast, the PBS NIR\\u0026thinsp;+\\u0026thinsp;group exhibited only a marginal temperature change from 32.0 to 34.6 ℃, underscoring the distinct specificity and efficacy of the nanocomposites. From the planktonic growth of bacteria in samples collected from the infected wound site after NIR irradiation treatment, we could see that Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI nanoparticles showed significant effective wound antibacterial therapy among the four treatments (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003eb). Images of wound repair at various time points (1, 3, 7, and 14 days) were taken, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ec. In comparison, the corresponding dynamics in the wound areas are graphically presented in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ed. Wound healing rates increased over time across all groups. However, compared with those in the other groups, the healing pace in the NIR-treated Ce6@ZIF-8-PDA/UBI group (group IV) markedly accelerated, with the number of infected wounds nearly vanishing by day 14 (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ee).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eDeeper insights into the healing process were obtained through histological analysis of the surrounding wound tissues. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ef, both the ZIF-8 and Ce6@ZIF-8 groups (Groups I and II) exhibited substantial numbers of neutrophils within the skin tissue, indicating persistent bacterial infection. Moreover, by day 14, these groups showed incomplete epidermal structures, accompanied by considerable defects. In contrast, the Ce6@ZIF-8-PDA group (Group III) exhibited notable fibroblast migration, albeit with incomplete epithelialization (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ef). Most impressively, the Ce6@ZIF-8-PDA/UBI group displayed a significant reduction in inflammation, with both epidermal and dermal structures nearly intact. This finding suggested superior wound healing efficiency. The results were supported by Masson's trichrome staining, which showed that by day 14, the Ce6@ZIF-8-PDA/UBI group displayed the most significant accumulation of collagen fibers (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ef). In summary, the experimental results underscore the remarkable efficacy of Ce6@ZIF-8-PDA/UBI treatment coupled with NIR irradiation in repairing full-thickness skin defects and \\u003cem\\u003eS. aureus\\u003c/em\\u003e infections \\u003cem\\u003ein vivo.\\u003c/em\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cdiv id=\\\"Sec23\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003eIn vivo peri-implant infection model\\u003c/h2\\u003e \\u003cp\\u003eTo further substantiate the impact of Ce6@ZIF-8-PDA/UBI nanoparticles on peri-implant infection, a rat femur peri-implantitis model was established. HE staining revealed substantial infiltration of inflammatory cells, including monocytes, neutrophils, and eosinophils, into the soft tissue in both the ZIF-8 and Ce6@ZIF-8 groups (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e7\\u003c/span\\u003e). Conversely, the Ce6@ZIF-8-PDA and Ce6@ZIF-8-PDA/UBI groups exhibited only sparse occurrences of monocytes, neutrophils, and eosinophils (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig7\\\" class=\\\"InternalRef\\\"\\u003e7\\u003c/span\\u003e). This observation implies a moderate inflammatory response and successful antibacterial efficacy. Consequently, \\u003cem\\u003ein vivo\\u003c/em\\u003e, under 808 nm NIR irradiation, the Ce6@ZIF-8-PDA/UBI nanoparticles demonstrated the most potent antibacterial effects.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec24\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBiosafety Assessment\\u003c/h2\\u003e \\u003cp\\u003eThe cytotoxicity of the ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles to L929 cells was assessed using the CCK assay (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig8\\\" class=\\\"InternalRef\\\"\\u003e8\\u003c/span\\u003ea). The cells were exposed to various concentrations of nanoparticles (10, 50, 100, 200, 300, 400, and 500 \\u0026micro;g/mL) for 24 hours. Analysis of cell viability revealed that cell survival rates exceeded 80% for concentrations lower than or equal to 400 \\u0026micro;g/mL (which surpassed the working concentration), indicating minimal toxicity of the carriers to L929 cells. These findings underscore the favorable biocompatibility of PDA-modified and UBI-loaded nanoparticles, suggesting their promising potential for drug delivery aimed at eradicating oral biofilms. Addressing potential nanoparticle toxicity remains a critical concern within the medical community and is closely linked to the safe clinical utilization of nanomaterials. In this study, hemolysis assays were conducted to provide additional insight into the impact of the prepared nanosystems on RBCs. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig8\\\" class=\\\"InternalRef\\\"\\u003e8\\u003c/span\\u003eb, the supernatant exhibited a vibrant red hue when suspended in deionized water, while the PBS groups (0 \\u0026micro;g/mL) retained their transparent appearance. The supernatant was transparent at particle concentrations of 10, 50, 100, 200, 300, 400, and 500 \\u0026micro;g/mL. There was no particle concentration-induced hemolysis rate greater than 5%. These findings indicated that the particles developed in this study are compatible when they are used at concentrations ranging from 0-500 \\u0026micro;g/mL. Following the implantation of titanium implants bearing bacterial biofilms and subsequent treatment with NIR-irradiated ZIF-8, Ce6@ZIF-8, Ce6@ZIF-8-PDA, and Ce6@ZIF-8-PDA/UBI nanoparticles, histological examination via HE staining of major organs (heart, liver, spleen, lung, and kidney) within a rat femur peri-implantitis model was performed. The analysis aimed to ascertain the presence of any discernible abnormalities in the major organs of rats subjected to various nanoparticle treatment (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig8\\\" class=\\\"InternalRef\\\"\\u003e8\\u003c/span\\u003ec). The results indicated the absence of conspicuous anomalies, reinforcing the favorable potential of Ce6@ZIF-8-PDA/UBI nanoparticles for prospective clinical applications.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe challenges posed by bacterial biofilm-associated infections are substantial in healthcare due to their heightened resistance to conventional antimicrobial agents. Recently, increased attention has been directed toward creating novel nanosystems designed to target bacteria within biofilms and disrupt the structural integrity of these biofilms. Nanoparticles offer several advantages, such as the ability to penetrate the biofilm matrix, direct targeting of bacterial cells within the biofilm, enhanced therapeutic outcomes, and reduced side effects. This study introduces an innovative approach, the Ce6@ZIF-8-PDA/UBI system, which achieves precise bacterial targeting and subsequent effective bacterial eradication through the synergistic application of both PDT and PTT.\\u003c/p\\u003e \\u003cp\\u003eThe strong adhesion of Ce6@ZIF-8-PDA/UBI to oral biofilms stems from the incorporation of PDA. PDA, a polymer akin to mussel attributes, is recognized for its robust adhesion owing to its diverse cationic amino acids [\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e]. Furthermore, PDA exhibits zwitterionic characteristics, with amine and phenolic hydroxyl groups juxtaposed to create positive charges at lower pH and negative charges at higher pH. Consequently, PDA-modified nanomaterials show an enhanced affinity for bacterial adsorption [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. For example, it has been reported that carboxymethyl chitosan/sodium alginate hydrogels coated with PDA can effectively eliminate biofilms and multidrug-resistant bacteria, aiding in wound healing [\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e]. Another study harnessed the inherent self-attaching ability of PDA to enhance biofilm lysis and bacterial elimination in \\u003cem\\u003eS. aureus\\u003c/em\\u003e biofilms grown on titanium substrates [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e]. PDA offers additional benefits, such as facile preparation, functionalization, biocompatibility, and excellent photothermal conversion efficiency. As an infrared-sensitive molecule, PDA has been employed to establish multifunctional nanoplatforms, yielding improved photothermal effects for bacterial and biofilm eradication [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. Consistently, it has been shown that a PDA coating enhances ZIF-8 stability and dispersion while providing high photothermal conversion efficiency [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe Ce6@ZIF-8-PDA/UBI nanosystem achieved outstanding antimicrobial performance due to its remarkable bacterial targeting capabilities. Various methods are employed for targeting bacteria, including antibodies, aptamers, and peptides. Antibodies are known for their high specificity and affinity for target antigens, but they often lack robust therapeutic efficacy [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Aptamers, while offering advantages such as low cytotoxicity, ease of preparation, and precise targeting abilities, face limitations due to the scarcity of available marketed products and potential instability \\u003cem\\u003ein vivo\\u003c/em\\u003e. On the other hand, peptides stand out as exceptional targeting agents in the battle against infections because of their straightforward synthesis and remarkable specificity [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e]. Peptides occupy a middle ground between antibodies and small molecular ligands, granting them a substantial binding area with receptors. This translates into significantly enhanced specificity and binding affinity compared to their molecular counterparts. Notably, antibacterial peptides execute their antibacterial functions through diverse strategies, such as disrupting peripheral membrane proteins, augmenting cell membrane permeability, and disrupting cell membrane organization. Nonetheless, challenges such as hemolytic toxicity, low protease stability, and a confined contact surface area somewhat hamper the potential applications of these materials. To address these challenges, the conjugation of peptides with nanoparticles has emerged as an exceptionally effective strategy [\\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e39\\u003c/span\\u003e]. To bolster bacterial targeting in this study, we incorporated UBI, an AMP-derived peptide renowned for its affinity and specificity for bacterial cell membranes [\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e]. Studies have shown that antibacterial peptides can target bacteria and induce bacterial cell membrane disruption to exert bactericidal effects [\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e]. Consequently, the UBI peptide has been utilized to target bacterium-infected sites, improving therapeutic outcomes [\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eAn additional attribute of the Ce6@ZIF-8-PDA/UBI system lies in its integration of both PDT and PTT modalities. PDT harnesses PSs to generate ROS, initiating bacterial eradication through membrane and DNA disruption. On the other hand, PTT employs photothermal agents to induce localized hyperthermia, achieving sterilization by denaturing bacterial proteins and causing irreversible bacterial damage [\\u003cspan citationid=\\\"CR43\\\" class=\\\"CitationRef\\\"\\u003e43\\u003c/span\\u003e]. While PDT and PTT each exhibit individual efficacy, their combined utilization enhances antibacterial potency. Thus, incorporating synergistic PDT/PTT effects offers a viable strategy for enhancing antibacterial efficiency [\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e]. In our research, we proposed the utilization of ZIF-8 nanoparticles loaded with the photosensitizer Ce6, integrating PDT and PTT for bacterial infection eradication. TEM analysis revealed that after Ce6@ZIF-8-PDA/UBI was subjected to NIR irradiation, the bacterial cell membranes were distorted, shrunken, severely damaged, or wholly disrupted, resulting in qualitative alterations to the cytoplasmic contents. These morphological anomalies appeared more pronounced than those observed with isolated PTT or PDT treatments. Additionally, live/dead staining corroborated these findings, with the most intense red fluorescence observed in the Ce6@ZIF-8-PDA/UBI/NIR\\u0026thinsp;+\\u0026thinsp;group, indicating significant compromise of bacterial cell membrane integrity, accompanied by damage and shrinkage. Based on these observations, we deduced that the antibacterial effect of Ce6@ZIF-8-PDA/UBI can be attributed to the generation of thermal and chemical energy. This energy disrupts the structural integrity of the cell membrane, triggers an increase in ROS within the bacteria, and results in cytoplasmic content leakage. Ultimately, these processes lead to loss of bacterial function and even bacterial death. Several investigations have also provided novel insights into the underlying antibacterial mechanism. PDT and PTT can expedite the transition of macrophages from the proinflammatory (M1) phenotype to the anti-inflammatory (M2) phenotype, implying that prevention of microbial invasion may involve both direct biofilm eradication via ROS and activation of the host immune response [\\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e]. Furthermore, research has demonstrated that mild PTT (\\u0026lt;\\u0026thinsp;45\\u0026deg;C) can induce heat shock proteins (HSPs), some of which play a crucial role in stimulating antigen-producing cells such as dendritic cells (DCs). This stimulation enhances the host immunological response, thereby facilitating tissue healing [\\u003cspan citationid=\\\"CR46\\\" class=\\\"CitationRef\\\"\\u003e46\\u003c/span\\u003e]. Thus, the potential immune responses underlying the Ce6@ZIF-8-PDA/UBI-mediated antibacterial process should be studied in the future.\\u003c/p\\u003e \\u003cp\\u003eA diverse range of bacterial strains were subjected to antibacterial experiments in this study. Initially, we showed the effective defense of Ce6@ZIF-8-PDA/UBI nanoparticles against infections caused by both gram-positive (\\u003cem\\u003eS. aureus\\u003c/em\\u003e) and gram-negative bacteria (\\u003cem\\u003eE. coli\\u003c/em\\u003e). Subsequently, to further substantiate the potential of Ce6@ZIF-8-PDA/UBI for oral biofilm elimination, we assessed its impact on \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e and \\u003cem\\u003eF. nucleatum\\u003c/em\\u003e, which are prominent bacterial species within the periodontal pocket. A series of experimental results consistently indicated the remarkable antibacterial properties of Ce6@ZIF-8-PDA/UBI both \\u003cem\\u003ein vitro\\u003c/em\\u003e and \\u003cem\\u003ein vivo\\u003c/em\\u003e. In our study, the superior antibacterial efficacy of the Ce6@ZIF-8-PDA/UBI system can be attributed to its adhesive properties, precise targeting of bacteria, and synergistic potential for PDT/PTT.\\u003c/p\\u003e \\u003cp\\u003eThe Ce6@ZIF-8-PDA/UBI system established in this study not only demonstrated robust antibacterial and biofilm resistance effects but also ensured the safety of the surrounding cells and tissues. CCK8 assays and HE staining of major organs (heart, liver, spleen, lung, and kidney) confirmed that the concentration of Ce6@ZIF-8-PDA/UBI utilized in our study met the cytotoxicity requirements. Notably, the Ce6@ZIF-8-PDA/UBI nanoparticles made their impact on only biofilms, limiting their toxicity to localized regions and inducing minimal photoinduced damage. Moreover, the photothermal temperature of this nanoparticle system, ranging from 38.5 to 56.1 ℃, could be regulated to be lethal for bacteria while remaining harmless to adjacent tissues. The Ce6@ZIF-8-PDA/UBI developed in this study holds significant potential as an effective antibacterial system for clinical applications.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eIn summary, using a synergistic approach involving PDT and PTT, we have successfully devised a novel Ce6@ZIF-8-PDA/UBI nanosystem designed to combat bacterial infections and eradicate biofilms. This inventive strategy enables precise bacterial targeting and enhanced penetration into oral biofilms. The combination of PDT and PTT potently inhibits biofilms while minimizing harm to organisms. Thus, this versatile system holds significant promise as a solution for tackling persistent biofilm infections.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003ctable border=\\\"0\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eEPSs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eExtracellular polymeric substances\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePDT\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePhotodynamic therapy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eROS\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eReactive oxygen species\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eCe6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eChlorin e6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eZIF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eZeolitic imidazolate framework\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePTT\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePhotothermal therapy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePDA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePolydopamine\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eNIR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eNear-infrared\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eUBI\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eUbiquicidine\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eMOF\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eMetal-organic framework\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eHMIM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003e2-methylimidazole\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eLE\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eLoading efficiency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eCLSM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eConfocal laser scanning microscopy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eTEM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eTransmission electron microscopy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eDLS\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eDynamic light scattering\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eFT-IR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eFourier transform infrared\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eXRD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eX-ray diffraction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eESR\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eElectron spin resonance\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eTEMP\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003e2,2,6,6-tetramethylpiperidine\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eTMB\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003e3,3\\u0026apos;,5,5\\u0026apos;-tetramethylbenzidine\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eSEM\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eScanning electron microscopy\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eCFU\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eColony-forming units\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePI\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003ePropidium iodide\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eFITC-ConA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eFITC-labeled concanavalin A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eHE\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eHematoxylin and eosin\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eSD\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eStandard deviation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eHSPs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eHeat shock proteins\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eDCs\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\"\\u003e\\n \\u003cp\\u003eDendritic cells\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eW.S., A.Z., X.W. and L.C. designed the research strategy. A.Z., X.W. and L.C. performed the materials construction and characterizations. W.S., A.Z., and X.W. performed the in vitro assays. Y.J., Z.L. and T.D. worked with the animal models and performed histochemical staining. Y.J., A.Z., X.W. and L.C. performed the statistical analysis, wrote and revised the manuscript. All the authors have read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis research was funded by the National Natural Science Foundation of China (82270953), the Shanghai Rising-Star Program (21QA1405400), and the Natural Science Foundation of Shanghai (22ZR1436400).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll the animal surgical experiments performed in this research were approved by the Animal Ethics Committee of Shanghai Ninth People\\u0026rsquo;s Hospital affiliated with Shanghai Jiao Tong University School of Medicine\\u0026nbsp;(License No. SCXK (Shanghai) 2012-0007).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors read and agreed to submit the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eGeng Z, Cao Z, Liu J. 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An injectable multifunctional hydrogel for eradication of bacterial biofilms and wound healing. Acta Biomater. 2023;161:112\\u0026ndash;33.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKharaziha M, Baidya A, Annabi N. Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing. Adv Mater. 2021;33:e2100176.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChen YH, Chuang EY, Jheng PR, Hao PC, Hsieh JH, Chen HL, et al. Cold-atmospheric plasma augments functionalities of hybrid polymeric carriers regenerating chronic wounds: In vivo experiments. Mater Sci Eng C Mater Biol Appl. 2021;131:112488.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"},{\"header\":\"Scheme \",\"content\":\"\\u003cp\\u003eScheme 1 is available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":false,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"journal-of-nanobiotechnology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"jnan\",\"sideBox\":\"Learn more about [Journal of Nanobiotechnology](http://jnanobiotechnology.biomedcentral.com)\",\"snPcode\":\"12951\",\"submissionUrl\":\"https://submission.nature.com/new-submission/12951/3\",\"title\":\"Journal of Nanobiotechnology\",\"twitterHandle\":\"@BioMedCentral\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Biofilm, Antibacterial, Phototherapy, ZIF-8, Ce6\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4522338/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4522338/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eThe escalating hazards posed by bacterial infections underscore the imperative for pioneering advancements in next-generation antibacterial modalities and treatments. Present therapeutic methodologies are frequently impeded by the constraints of insufficient biofilm infiltration and the absence of precision in pathogen-specific targeting. In this current study, we have used chlorin e6 (Ce6), zeolitic imidazolate framework-8 (ZIF-8), polydopamine (PDA), and UBI peptide to formulate an innovative nanosystem meticulously engineered to confront bacterial infections and effectually dismantle biofilm architectures through the concerted mechanism of photodynamic therapy (PDT)/photothermal therapy (PTT) therapies, including in-depth research, especially for oral bacteria and oral biofilm. Ce6@ZIF-8-PDA/UBI nanosystem, with effective adhesion and bacteria-targeting, affords a nuanced bacterial targeting strategy and augments penetration depth into oral biofilm matrices. The Ce6@ZIF-8-PDA/UBI nanosystem potentiated bacterial binding and aggregation. Upon exposure to near-infrared (NIR) irradiation, Ce6@ZIF-8-PDA/UBI showed excellent antibacterial effect on \\u003cem\\u003eS. aureus, E. coli, F. nucleatum\\u003c/em\\u003e, and \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e and exceptional light-driven antibiofilm activity to \\u003cem\\u003eP. gingivalis\\u003c/em\\u003e biofilm, which was a result of the efficient bacterial localization mediated by PDA/UBI, as well as the PDT/PTT facilitated by Ce6/PDA interactions. Collectively, these versatile nanoplatforms augur a promising and strategic avenue for controlling infection and biofilm, thereby holding significant potential for future integration into clinical paradigms. The original application of the developed nanosystem in oral biofilms also provides a new strategy for effective oral infection treatment.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Photodynamic and photothermal bacteria targeting nanosystems for synergistically combating bacteria and biofilms\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-06-24 05:46:35\",\"doi\":\"10.21203/rs.3.rs-4522338/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision 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