Facile synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure

Facile synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure | 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 Facile synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure Xuzhi Shi, Yifeng Yu, Ruifa Yu, Ning Wang, Wei Lu, Xiaolin Han, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4556757/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Aug, 2024 Read the published version in Journal of Porous Materials → Version 1 posted 11 You are reading this latest preprint version Abstract Herein, copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure (CuS/tHMONs) are successfully synthesized. The resulting CuS/tHMONs nanospheres exhibit a uniform diameter of 340 nm, mesoporous channels with a diameter of 3.8 nm, large pore volume, and triply separated cavities. High-angle annular dark-field scanning electron microscopy (HAADF-STEM) images confirm the presence of a high content of CuS nanoparticles within the CuS/tHMONs composite nanospheres. Moreover, the CuS/tHMONs nanospheres demonstrate high photothermal conversion efficiency and excellent photothermal stability. In vitro experiments reveal excellent biocompatibility of the CuS/tHMON nanospheres, and cytotoxic assays demonstrate their effectiveness in killing cancer cells through photothermal therapy. mesoporous organosilica composite nanospheres hollow structure triple-shell photothermal Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Mesoporous materials have attracted significant attention due to their remarkable characteristics, including high surface area, large pore volume, and uniform mesopores [ 1 – 3 ]. These materials serve as desirable matrices for constructing functional composites by incorporating metals and metal oxides, which hold great promise in catalysis, sensing, and biomedicine [ 4 – 8 ]. Synthesis of functional mesoporous composites with controlled morphologies and architectures is crucial for their practical applications [ 9 – 11 ]. Mesoporous composites with different morphologies, including sphere [ 12 – 14 ], heterostructure [ 15 – 17 ], and hollow structures [ 18 – 20 ] have been successfully synthesized. The structures offer the mesoporous composites with unique properties and potential applications in various fields. Notably, hollow materials have attracted increasing attention as platforms for preparation of advanced functional composites, thanks to their unique features such as large cavity and heterogeneous interfaces [ 21 – 25 ]. For instance, Wu et al. achieved the integration of multi-shelled mesoporous silica nanoparticles with gold nanoparticles through electrostatic adsorption [ 26 ]. Li et al. reported enzyme-loaded multi-shelled metal-organic frameworks using an epitaxial shell-by-shell overgrowth method, which acted as nanoreactors to enhance catalytic efficiency in incompatible tandem biocatalytic processes [ 27 ]. However, the synthesis of multi-shelled mesoporous composites still faces challenges including poor product homogeneity and time-consuming procedures. In our previous work, we successfully prepared hollow mesoporous organosilica nanoparticles (HMONs) with multiple shells using a multi-interface transformation strategy [ 28 ]. Moreover, we hybridized HMONs with organic groups with coordination ability to metal ions by employing different organosilanes as precursors [ 29 , 30 ]. These findings have inspired us to pursue the preparation of functional multi-shelled mesoporous composites. Herein, we successfully prepared CuS nanoparticles loaded mesoporous organosilica nanospheres with triple-shelled hollow sturcture (CuS/tHMONs). The synthesis procedures involved the preparation of amino-hybridized triple-shelled hollow mesoporous organosilica nanoparticles through a multiple-interface transformation approach, followed by an in situ growth of CuS nanoparticles on the mesoporouos shells. The resulting CuS/tHMONs exhibited a well-defined triple-shell hollow structure, uniform size (340 nm), and mesoporous channels with a diameter of 3.80 nm. In addition, the CuS/tHMONs exhibited excellent photothermal conversion efficiency (18.38%) and good photothermal stability under 808 nm laser irradiation. In vitro cytotoxicity assays revealed that the CuS/tHMONs possess excellent biocompatibility and excellent efficacy in photothermal therapy against human osteosarcoma 143B cells. 2. Experimental 2.1. Materials Cetyltrimethylammonium bromide (CTAB) (99 wt%), aqueous ammonia solution (25–28 wt%), tetraethyl orthosilicate (TEOS), copper chloride dihydrate, hydrochloric acid, and anhydrous ethanol were obtained from Sinopharm Chemical Reagents Co., Ltd. (Shanghai, China). (3-Aminopropyl)triethoxysilane and 1,2-bis(triethoxysilyl)ethane (BTSE) were purchased from Sigma-Aldrich (Shanghai, China). Sodium sulfide nonahydrate and sodium citrate were obtained from Shanghai Macklin Biochemical Co., Ltd. (Shanghai, China). Minimum essential medium (MEM) and fetal bovine serum (FBS) were purchased from Grand Island Biological Company (NY, USA). Phosphate-buffered saline and Cell Counting Kit-8 were acquired from Lanjiike Technology Co., Ltd. (Hefei, China). 2.2. Synthesis The synthesis of amino-hybridized triple-shelled hollow mesoporous organosilica nanoparticles (tHMONs-NH 2 ) followed the typical procedure outlined below: First, 0.16 g of CTAB was dissolved in a mixed solution containing 1 mL of concentrated ammonia aqueous solution (25 wt%), 30 mL of ethanol, and 75 mL of water at 35°C. After 1 h, a mixture of APTES (0.625 mL), BTSE (0.0625 mL), and TEOS (0.125 mL) was rapidly added under vigorous stirring. The resulting mixture was stirred at 35°C for 24 h. Afterwards, the mesostructured hybridized nanospheres were collected by centrifugation at 10,000 rpm for 10 min and washed three times with ethanol. The obtained mesostructured nanospheres were then dispersed again in a mixed solution of CTAB (0.16 g), deionized water (75 mL), and ethanol (30 mL). After 30 min of ultrasonic dispersion, 1 mL of concentrated aqueous ammonia solution was added, and the mixture was placed in a 35°C water bath for 1 h. The same doses of TEOS, BTSE, and APTES used in the first step were added and stirred for an additional 24 h, resulting in two-layer mesostructured nanospheres. The same procedure and experimental conditions were repeated to obtain three-layer mesostructured hybridized nanospheres. The three-layer mesostructured nanospheres were then dispersed in 30 mL of water and transferred to a stainless-steel autoclave lined with Teflon. The autoclave was placed in an air flow electric oven set to 140°C for 5 h. The resulting product was collected by centrifugation and washed with ethanol. The CTAB in the product was extracted three times in a solution comprising 200 mL of ethanol and 400 µL of concentrated HCl (37%) for 12 h, and tHMONs-NH 2 was obtained. To load CuS nanoparticles in the tHMONs-NH 2 , 5 mL of tHMONs-NH 2 (0.7 mg/mL) was mixed with 2.5 mL of CuCl 2 ·2H 2 O (20 mM). After shaking for 12 h, 2.5 mL of sodium citrate (13.6 mM) and 0.2 mL of Na 2 S·9H 2 O (0.25 mM) were added to the mixture and stirred at room temperature for 10 min (600 rpm). The mixed solution was further stirred at 80°C for 10 min and then immersed in an ice bath for 20 min. Finally, the resulting CuS/tHMONs were collected by centrifugation at 10,000 rpm for 10 min and washed with ethanol three times. 2.3. Photothermal performance First, CuS/tHMONs were dispersed in 200 µL of deionized water and irradiated with an 808 nm laser at a power density of 1.25 W/cm 2 for 5 min. Additionally, CuS/tHMONs dispersed in water were subjected to irradiation with an 808 nm laser at various power densities. For the photothermal stability test, 200 µL aqueous solution of CuS/tHMONs (200 µg/mL) was irradiated with a 1.25 W/cm 2 laser at 808 nm for 5 cycles. Each cycle consisted of a heating time of 3 min and a cooling time of 6 min. The temperature of the solution was recorded using an infrared camera from Fotric Company and Analyzir software. The photothermal conversion efficiency of CuS/tHMONs was calculated using the following formula: $$\varvec{\eta }=\frac{hs\left({T}_{max}-{T}_{amb}\right)-{Q}_{0}}{I(1-{10}^{-A})}\times 100\%$$ In this formula, h is the heat transfer coefficient, S is the vessel surface area, T max is the maximum temperature under light radiation, T amb is the ambient temperature, I is the laser power, A is the absorbance of the sample solution at 808 nm, and Q 0 is the water and heat loss from light absorbed by the sample cell. hS was calculated according to the following formula: $$hS=\frac{{m}_{D}{C}_{D}}{{\tau }_{s}}$$ where m D and C D are the mass and heat capacity of deionized water (4.2 J/g), respectively, and τ s is the system time constant, calculated according to the following formula: $$t={\tau }_{s}In\frac{T-{T}_{amb}}{{T}_{max}-{T}_{amb}}$$ where t is the time value point of the cooling stage and T is the real-time temperature corresponding to each time value point. 2.4. Cytotoxicity assay and photothermal therapy In the cell viability assay, 143B osteosarcoma cells were seeded in 96-well plates at a density of 50,000 cells per well in 50 µL of MEM supplemented with 10% FBS. The plates were then placed in a 5% CO 2 incubator at 37°C (Thermo Fisher HERA cell 150i incubator). After 12 h of cell seeding, the medium was replaced with fresh medium containing different concentrations of the materials being tested. The concentrations used were as follows: CuS/tHMONs: 0, 10, 20, 30, 40, and 50 µg/mL; tHMONs-NH 2 : 0, 10, 20, 40, 80, and 160 µg/mL. Cell viability was assessed using a CCK8 assay. Specifically, 10 µL of CCK8 solution was added to each well at 24 h and 48 h after treatment. The plates were then incubated for a specified period, and the optical density (OD) at 450 nm was measured using a Multiskan FC-type plate reader from Thermo Fisher. The measurements were performed in triplicate for each sample (n = 6). For the photothermal therapy assay, the same concentrations of CuS/tHMONs and tHMONs-NH 2 mixed media were placed in separate wells and incubated for 24 h. The cells were then subjected to irradiation under a power density of 1.5 W/cm 2 for 5 min. Following the treatment, cell cytotoxicity was assessed using the CCK8 assay. 2.5. Characterization Transmission electron microscopy (TEM) images were obtained at 100 kV on a Hitachi HT7700 microscope (Tokyo, Japan). High-resolution TEM (HR-TEM) images were captured using an FEI Talos F200x electron microscope (Hillsboro, USA). Scanning electron microscopy (SEM) images were captured using a Hitachi-S4800 microscope (Tokyo, Japan) at 5 kV and 10 mA. High-angle annular dark-field scanning electron microscopy (HAADF-STEM) and energy dispersive X-ray (EDX) images of the CuS/tHMONs were obtained on an FEI Talos F200X (Hillsboro, USA). The Fourier transform infrared (FT-IR) spectra were measured using a NEXUS870 infrared spectrometer (Madison, USA). The valence states of the copper and sulfur in CuS/tHMONs were tested using an Axis Supra X-ray photoelectron spectroscopy (XPS) from Kratos (Manchester, UK). Dynamic light scattering measurements were performed using a ZetaPLAS analyzer from Brookhaven (New York, USA). The nitrogen adsorption-desorption isotherms of tHMONs-NH 2 and CuS/tHMONs were measured at -196 ℃ using a V-Sorb 2800P specific surface area analyzer. (Beijing, Chian). The pore size distribution was calculated using the Barret-Joyner-Halenda (BJH) method. 3. Results and Discussion 3.1. Synthesis and characterization Triple-shelled hollow mesoporous nanospheres hybridized with amino groups were first synthesized using a multiple-interface transformation approach [ 29 ]. TEM images revealed that the prepared tHMONs-NH 2 has a uniform diameter of approximately 340 nm with three hollow chambers and a smooth surface (Fig. 1 a, b). After loading CuS nanoparticles in situ, TEM images showed that the CuS/tHMONs maintained the triple-shell hollow structure and spherical shape (Fig. 1 c). The surface of CuS/tHMONs appeared rougher due to the presence of tightly anchored CuS nanoparticles. Low-magnification SEM images indicated the uniform size and morphology of CuS/tHMONs (Fig. 1 d). High-magnification SEM images revealed a rough surface of CuS/tHMONs, attributed to a layer of nanoparticles firmly attached to the surface (Fig. 1 e). HR-TEM images further confirmed the successful loading of CuS within CuS/tHMONs, as evidenced by the lattice spacing of 0.33 nm corresponding to the interplanar spacing of CuS nanodots with hexagonal phase (Fig. S1 a and Fig. 1 f). The hydrodynamic diameters of the tHMONs-NH 2 and CuS/tHMONs were measured to be 344 nm and 352 nm, respectively (Fig. 1 g). The zeta potentials of tHMONs-NH 2 and CuS/tHMONs were measured to be 37.4 ± 0.24 mV and − 16.27 ± 0.84 mV, respectively (Fig. 1 h). These results demonstrate that CuS nanodots were effectively attached to the positively charged tHMONs-NH 2 , resulting in a change in surface charge. Overall, the characterization results provide evidence for the synthesis of triple-shell hollow mesoporous nanoparticles hybridized with amino groups (tHMONs-NH 2 ) and subsequent successful loading of CuS nanoparticles to form CuS/tHMONs, with the CuS nanoparticles tightly anchored on the tHMONs. The components of CuS/tHMONs and tHMONs-NH 2 were analyzed using FT-IR spectroscopy. The FT-IR spectra of CuS/tHMONs and tHMONs-NH 2 exhibited characteristic peaks at 1414 cm -1 indicative of the vibration of the C-H bond in the CH 2 -CH 2 group and peaks at 3445 cm -1 corresponding to the vibration of the N-H bond in the -NH 2 group (Fig. 1 i). These peaks confirmed the presence of the organosilica precursors APTES and BTSE in the products, indicating their successful condensation. XPS analysis of CuS/tHMONs revealed three signals at 931.6 eV, 283.4 eV, and 168.6 eV, corresponding to Cu, C, and S, respectively (Fig. 2 a). The XPS curve of Cu 2p showed characteristic peaks of Cu 2p1/2 and Cu 2p3/2 at 950.5 eV and 930.6 eV, respectively, confirming that the valence state of copper in CuS/tHMONs was + 2 (Fig. 2 b). The nitrogen adsorption-desorption isotherms of tHMONs-NH 2 and CuS/tHMONs exhibited a type IV curve with a hysteresis loop, indicating a typical mesoporous structure (Fig. 2 c). The pore size distribution, calculated using the BJH method, revealed an uniform mesopore size of approximately 3.8 nm for both tHMONs-NH 2 and CuS/tHMONs (Fig. 2 d). This indicates that the loading of CuS nanoparticles did not significantly affect the mesoporous structure or pore size of the nanoparticles. In summary, the FT-IR spectroscopy confirmed the presence of the organosilica precursors in tHMONs-NH 2 and CuS/tHMONs. The XPS analysis confirmed the presence of copper and sulfur in CuS/tHMONs, with copper in the + 2 valence state. The nitrogen adsorption-desorption isotherms and pore size distribution demonstrated the mesoporous nature of both tHMONs-NH 2 and CuS/tHMONs, with an uniform pore size of approximately 3.8 nm after the loading of CuS nanoparticles. To investigate the distribution of CuS nanoparticles within the structure of CuS/tHMONs, HR-TEM and energy-dispersive X-ray spectroscopy (EDX) were employed. High-angle annular dark-field (HAADF) images revealed that the CuS/tHMONs maintained a well-defined triple-shell hollow structure, indicating that the in situ synthesis of CuS did not disturb the hollow structure (Fig. 3 a). Elemental mapping images of CuS/tHMONs demonstrated the distribution of Cu, C, N, Si, O, and S elements within the three shells (Fig. 3 b‒g). To further analyze the spatial distribution of these elements, elemental line scan curves were performed for Cu, S, and Si (Fig. S2a). The Si signals were observed at 26 nm, 42 nm, and 82 nm, corresponding to the positions of the three shells in the range of 0 to 100 nm. The signals of both Cu and S were most prominent at 26 nm, indicating that the CuS nanoparticles were primarily adsorbed on the outermost shell layer (Fig. S2b). This observation is attributed to the fact that Cu 2+ at the outermost shell consumed a significant amount of S 2- during the reaction, while a relatively small amount of S 2- diffused into the cavity of tHMONs-NH 2 through the mesoporous channels. In summary, the HR-TEM and EDX analysis confirmed that CuS/tHMONs maintained a triple-shell hollow structure. The elemental mapping images provided visual evidence of the distribution of Cu, C, N, Si, O, and S elements within the three shells of the nanospheres. 3.2 Photothermal performance The UV‒vis curve of CuS/tHMONs exhibited a broad peak at near-infrared wavelengths compared to tHMONs-NH 2 (Fig. 4 a). This indicates that CuS/tHMONs has enhanced light absorption in the near-infrared region. The photothermal effects of CuS/tHMONs under near-infrared (NIR) irradiation were studied by measuring the temperature profiles of CuS/tHMONs at various concentrations (0‒300 µg/mL) under laser irradiation (808 nm, 1.25 W/cm 2 ). The results showed that CuS/tHMONs increase the temperature from 25°C to 45°C at a concentration of 300 µg/mL, and the temperature profiles displayed a concentration-dependent behavior (Fig. 4 b). In contrast, water exhibited negligible temperature change (< 3°C) under the same conditions. Additionally, the heating curve of CuS/tHMONs exposed to different laser powers demonstrated a positive correlation between temperature and laser power density (Fig. 4 c). The photothermal stability of CuS/tHMONs was evaluated by subjecting the nanospheres to five successive irradiation-heating and natural cooling cycles (cycle time: 180 s). The photothermal stability curve showed no significant reduction in temperature after each cycle, indicating excellent photothermal stability (Fig. 4 d). Thermal images of CuS/tHMONs further confirmed the time and concentration-dependent photothermal conversion of the nanospheres (Fig. 4 e‒f). The system time constant (τs) was determined to be 238 s by analyzing the linear regression curve between the cooling stage of CuS/tHMONs and the negative natural logarithm of the driving force temperature. Based on this analysis, the photothermal conversion efficiency of CuS/tHMONs was calculated to be approximately 18.38% (Fig. 4 g‒h), indicating their efficient photothermal conversion property. In summary, the UV‒vis analysis revealed enhanced light absorption in the near-infrared region for CuS/tHMONs. The nanospheres exhibited excellent photothermal stability, maintaining their temperature increase after multiple irradiation-heating cycles. The photothermal effects of CuS/tHMONs were concentration-dependent, with significant temperature elevation under NIR irradiation. 3.3 Cytotoxicity assay and photothermal property To assess the potential biological applications of CuS/tHMONs, the cytotoxicity and photothermal therapy effects of the nanocomposites were evaluated in 143B osteosarcoma cells. The cytotoxicity assay demonstrated that cell viability remained above 80% when the cells were incubated with tHMONs-NH 2 or CuS/tHMONs for 24 or 48 h, indicating good biocompatibility of the triple-shell mesoporous nanospheres (Fig. 5 a, b). Under laser irradiation, the cell viability of 143B cells incubated with tHMONs-NH 2 remained above 80% (Fig. 5 c). In contrast, the viability of 143B cells incubated with CuS/tHMONs exhibited a clear concentration-dependent response (Fig. 5 d). At a concentration of 50 µg/mL of CuS/tHMONs, only approximately 40% of the cells survived, indicating the excellent photothermal therapy effect of CuS/tHMONs. In summary, the cytotoxicity assay demonstrated the good biocompatibility of CuS/tHMONs, with cell viability above 80% after incubation. However, under laser irradiation, the photothermal therapy effect of CuS/tHMONs was evident, indicating the potential of CuS/tHMONs for effective photothermal therapy in 143B osteosarcoma cells. 4. Conclusion In conclusion, the synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure (CuS/tHMONs) was successfully achieved. These nanocomposites exhibited a spherical shape, triple-shell structure, uniform size (340 nm), and well-defined mesoporous channels (3.80 nm). HAADF images and element mapping confirmed the presence of a significant amount of CuS loaded within the frameworks. The photothermal conversion efficiency of CuS/tHMONs was calculated to be 18.38%, indicating their efficient conversion of light into heat. Photothermal experiments demonstrated that CuS/tHMONs possessed excellent photothermal stability. Furthermore, cell viability analysis revealed that the CuS/tHMONs exhibited good biocompatibility in the absence of laser irradiation. When subjected to 808 nm laser irradiation, CuS/tHMONs exhibited a notable inhibitory effect against human osteosarcoma 143B cells, indicating their potential for tumor photothermal treatment. In summary, the synthesized CuS/tHMONs composite nanospheres displayed a well-defined structure, efficient photothermal conversion, excellent photothermal stability, good biocompatibility, and demonstrated a promising inhibitory effect on osteosarcoma cells under laser irradiation. These findings highlight the preparation of mesoporous composites with mutil-shelled hollow structures and the potential for applications in tumor photothermal therapy. Declarations Author contributions Xuzhi Shi: Writing–original draft. Yifeng Yu: Biological experiments. Ruifa Yu: Materials synthesis. Ning Wang: Writing–original draft. Wei Lu: Biological experiments, Writing–original draft. Xiaolin Han: Materials synthesis. Tangyao Sun: Materials synthesis. Pengcheng Li: Conceptualization, Writing–review and editing. Xiaodan Su: Characterization. Zhaogang Teng: Writing–review and editing. Ying Liu: Writing–review and editing. Funding This work was supported by the National Natural Science Foundation of China (81971675, 21603106), Natural Science Foundation of Hubei Province(2022CFB973), Program for Science and Technology Development of Wenzhou (Y20210226) and Scientific Research Fund of Zhejiang Provincial Education Department (Y202250265). X.S. and Y.Y. authors contributed equally to this work. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Data Availability No data was used for the research described in the article. References T.C. Zhao, A. Elzatahry, X.M. Li, D.Y. Zhao, Single-micelle-directed synthesis of mesoporous materials. Nat. Rev. Mater. 4, 775-791 (2019). https://doi.org/10.1038/s41578-019-0144-x S.L. Suib, A review of recent developments of mesoporous materials. Chem. Rec. 17(12), 1169-1183 (2017). https://doi.org/10.1002/tcr.201700025 W. Zhang, Y. Tian, H.L. He, L. Xu, W. Li, D.Y. Zhao, Recent advances in the synthesis of hierarchically mesoporous TiO2 materials for energy and environmental applications. Natl. Sci. Rev. 7 (11), 1702-1725 (2020). https://doi.org/10.1093/nsr/nwaa021 L.H. Zu, W. Zhang, L.B. Qu, L.L. Liu, W. Li, A. Yu, D.Y. Zhao, Mesoporous materials for electrochemical energy storage and conversion. Adv. Energy Mater. 10 38), 2002152 (2020). https://doi.org/10.1002/aenm.202002152 L.L. Duan, C.Y. Wang, W. Zhang, B. Ma, Y.H. Deng, W. Li, D.Y. Zhao, Interfacial assembly and applications of functional mesoporous materials. Chem. Rev. 121 (23), 14349-14429 (2021). https://doi.org/10.1021/acs.chemrev.1c00236 W. Li, J. Liu, D.Y. Zhao, Mesoporous materials for energy conversion and storage devices. Nat. Rev. Mater. 1 (6), 1-17 (2016). https://doi.org/10.1038/natrevmats.2016.23 J.Z. Yao, N.R. Sun, C.H. Deng, Recent advances in mesoporous materials for sample preparation in proteomics research. Trends Anal. Chem. 99, 88-100 (2018). https://doi.org/10.1016/j.trac.2017.11.016 P.P. Qiu, B. Ma, C.T. Hung, W. Li, D.Y. Zhao, Spherical mesoporous materials from single to multilevel architectures. Acc. Chem. Res. 52 (10), 2928-2938 (2019). R.K. Kankala, H.B. Zhang, C.G. Liu, K.R. Kanubaddi, C.H. Lee, S.B. Wang, W.G. Cui, H. A. Santos, K.L. Lin, A.Z. Chen, Metal species-encapsulated mesoporous silica nanoparticles, current advancements and latest breakthroughs. Adv. Funct. Mater. 29 (2019), 1902652 (2019). https://doi.org/10.1021/acs.accounts.9b00357 H. Liu, Y. Feng, D. Chen, C.Y. Li, P.L. Cui, J. Yang, Noble metal-based composite nanomaterials fabricated via solution-based approaches. J. Mater. Chem. A. 3 (7), 3182-3223 (2015). https://doi.org/10.1039/C4TA05801A P. Karami, S.S. Khasraghi, M. Hashemi, S. Rabiei, A. Shojaei, Polymer/nanodiamond composites-a comprehensive review from synthesis and fabrication to properties and applications. Adv. Colloid Interface Sci. 269, 122-151 (2019). https://doi.org/10.1016/j.cis.2019.04.006 Z.H. Zhang, C.H. Liu, J.H. Bai, C.C. Wu, Y. Xiao, Y.H. Li, J. Zheng, R.H. Yang, W.H. Tan, Silver nanoparticle gated, mesoporous silica coated gold nanorods (AuNR@MS@AgNPs), low premature release and multifunctional cancer theranostic platform. ACS Appl. Mater. Interfaces. 7 (11), 6211-6219 (2015). https://doi.org/10.1021/acsami.5b00368 H.B. Zou, J.Y. Dai, J.Q Suo, R. Ettelaie, Y. Li, N. Xue, R.W. Wang, H.Q. Yang, Dual metal nanoparticles within multicompartmentalized mesoporous organosilicas for efficient sequential hydrogenation. Nat. Commun. 12 (1), 1-11 (2021). https://doi.org/10.1038/s41467-021-25226-x W.N. Zeng, D. Wang, Q.P. Yu, Z.P. Yu, H.Y. Wang, C.Y. Wu, S.W. Du, X.Y. Chen, J.F. Li, Z.K. Zhou, Y. Zeng, Y. Zhang, Near-infrared light-controllable multifunction mesoporous polydopamine nanocomposites for promoting infected wound healing. ACS Appl. Mater. Interfaces. 14 (2), 2534-2550 (2022). https://doi.org/10.1021/acsami.1c19209 M.L. Liu, L. Chen, Z.W. Zhao, M.C. Liu, T.C. Zhao, Y.Z. Ma, Q.Y. Zhou, Y. S. Ibrahim, A. A. Elzatahry, X.M. Li, D.Y. Zhao, Enzyme-based mesoporous nanomotors with near-infrared optical brakes. J. Am. Chem. Soc. 144 (9), 3892-3901 (2022). https://doi.org/10.1021/jacs.1c11749 Y.X. Ji, X.K. Lin, H.Y. Zhang, Y.J. Wu, J.B. Li, Q. He, Thermoresponsive polymer brush modulation on the direction of motion of phoretically driven janus micromotors. Angew. Chem. Int. Ed. 58 (13), 4184-4188 (2019). https://doi.org/10.1002/anie.201812860 Y. Xing, M.Y. Zhou, T.L. Xu, S.S. Tang, Y. Fu, X. Du, L. Su, Yongqiang Wen, Xueji Zhang, Tianyi Ma, Core@satellite Janus nanomotors with pH‐responsive multi‐phoretic propulsion. Angew. Chem. Int. Ed. 59 (34), 14368-14372 (2020). https://doi.org/10.1002/anie.202006421 H.J. Wang, J. Tao, C.L. Xu, Y. Tian, G.M. Lu, B. Yang, Z.G. Teng, Flexible CuS-embedded human serum albumin hollow nanocapsules with peroxidase-like activity for synergistic sonodynamic and photothermal cancer therapy. Nanoscale, 14 (27), 9702-9714 (2022). P. Xu, Z.G. Wu, W.Dai, Y. Wang, M.K. Zheng, X.D. Su, Z.G. Teng, Synthesis of multiple Ag nanoparticles loaded hollow mesoporous carbon spheres for highly efficient and recyclable catalysis. Microporous Mesoporous Mater. 314, 110856 (2021). https://doi.org/10.1016/j.micromeso.2020.110856 N. Lu, W.P. Fan, X. Yi, S. Wang, Z.T. Wang, R. Tian, O. Jacobson, Y.J. Liu, B.C. Yung, G.F. Zhang, Z.G. Teng, K. Yang, M.M. Zhang, G. Niu, G.G. Lu, X.Y. Chen, Biodegradable hollow mesoporous organosilica nanotheranostics for mild hyperthermia-induced bubble-enhanced oxygen-sensitized radiotherapy. ACS Nano. 12 (2), 1580-1591 (2018). https://doi.org/10.1021/acsnano.7b08103 J.Y. Wang, H.J. Tang, H. Wang, R.B. Yu, D. Wang, Multi-shelled hollow micro-/nanostructures, promising platforms for lithium-ion batteries. Mater. Chem. Front. 1 (3), 414-430 (2017). https://doi.org/10.1039/C6QM00273K X.J. Wang, J. Feng, Y.C. Ba, Q. Zhang, Y.D. Yin, Synthesis, properties, and applications of hollow micro-/nanostructures. Chemical Reviews. 116 (18), 10983-11060 (2016). https://doi.org/10.1021/acs.chemrev.5b00731 Wang J, Wan J, Yang N, et al. Hollow multishell structures exercise temporal–spatial ordering and dynamic smart behaviour. Nat. Rev. Chem. 4(3), 159-168 (2020). https://doi.org/10.1038/s41570-020-0161-8 J.Y. Wang, J.W. Wan, N.L. Yang, Q. Li, D. Wang, A versatile ligand-assisted cooperative template method to synthesize multi-shelled mesoporous hollow metal hydroxide and oxide nanospheres as catalytic reactors. Nano Res. 14, 3260-3266 (2021). https://doi.org/10.1007/s12274-021-3403-2 R. Amal, Promising hollow multi-shelled structures, discovering the temporal-spatial ordering. Natl. Sci. Rev. 7 (11), 1763-1764 (2020). https://doi.org/10.1093/nsr/nwaa106 L. Wu, H.J. Zhang, M.H. Wu, Y.F. Zhong, X.W. Liu, Z. Jiao, Dual-templating synthesis of multi-shelled mesoporous silica nanoparticles as catalyst and drug carrier. Microporous Mesoporous Mater. 228 (1), 318-328 (2016). https://doi.org/10.1016/j.micromeso.2016.03.040 T.T. Man, C.X. Xu, X.Y. Liu, D. Li, C.K. Tsung, H. Pei, Y. Wan, L. Li, Hierarchically encapsulating enzymes with multi-shelled metal-organic frameworks for tandem biocatalytic reactions. Nat. Commun. 13 (1), 1-12 (2022). https://doi.org/10.1038/s41467-022-27983-9 Z.G. Teng, X.D. Su, Y.Y. Zheng, J.J. Zhang, Y. Liu, S.J. Wang, J. Wu, G.T. Chen, J.D. Wang, D.Y. Zhao, G.G. Lu, A facile multi-interface transformation approach to monodisperse multiple-shelled periodic mesoporous organosilica hollow spheres. J. Am. Chem. Soc. 137 (24), 7935-7944 (2015). https://doi.org/10.1021/jacs.5b05369 R.F. Yu, J. Tao, L.X. Shao, W. Lu, J.J Zhao, R. Tang, J. Li, Z.G. Teng, Facile synthesis of hybridized triple-shelled hollow mesoporous organosilica nanoparticles. J. Taiwan Inst. Chem. Eng. 131, 104122 (2022). https://doi.org/10.1016/j.jtice.2021.10.022 Z.G. Teng, J.J. Zhang, W. Li, Y.Y. Zheng, X.D. Su, Y.X. Tang, M. Dang, Y. Tian, L.H. Yuwen, L.X Weng, G.M Lu, L.H Wang, Facile synthesis of yolk-shell‐structured triple‐hybridized periodic mesoporous organosilica nanoparticles for biomedicine. Small 12 (26), 3550-3558 (2016). https://doi.org/10.1002/smll.201600616 Additional Declarations No competing interests reported. Supplementary Files SupportingInformation.docx Cite Share Download PDF Status: Published Journal Publication published 22 Aug, 2024 Read the published version in Journal of Porous Materials → Version 1 posted Editorial decision: Revision requested 07 Jul, 2024 Reviews received at journal 29 Jun, 2024 Reviews received at journal 22 Jun, 2024 Reviewers agreed at journal 21 Jun, 2024 Reviewers agreed at journal 15 Jun, 2024 Reviewers agreed at journal 13 Jun, 2024 Reviewers agreed at journal 13 Jun, 2024 Reviewers invited by journal 13 Jun, 2024 Editor assigned by journal 11 Jun, 2024 Submission checks completed at journal 11 Jun, 2024 First submitted to journal 10 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4556757","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317763903,"identity":"7b302198-d219-4040-b972-b7277a18a417","order_by":0,"name":"Xuzhi Shi","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Xuzhi","middleName":"","lastName":"Shi","suffix":""},{"id":317763904,"identity":"b7736262-4236-4c8d-8b31-25eccd7facc6","order_by":1,"name":"Yifeng Yu","email":"","orcid":"","institution":"Zhongnan Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Yifeng","middleName":"","lastName":"Yu","suffix":""},{"id":317763905,"identity":"6156dce2-18c7-4de3-ac89-50f9328869a3","order_by":2,"name":"Ruifa Yu","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Ruifa","middleName":"","lastName":"Yu","suffix":""},{"id":317763906,"identity":"5d1ce8cb-29f2-45dc-95c6-23d355ae2f52","order_by":3,"name":"Ning Wang","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Wang","suffix":""},{"id":317763907,"identity":"b4eb0055-a404-4c2d-ad17-9632166d250d","order_by":4,"name":"Wei Lu","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Lu","suffix":""},{"id":317763908,"identity":"8887fb83-ef63-4bfa-8a6b-4201c0e28abe","order_by":5,"name":"Xiaolin Han","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Han","suffix":""},{"id":317763909,"identity":"d0fe070b-74e7-40ef-927c-5895d6f9380a","order_by":6,"name":"Tangyao Sun","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Tangyao","middleName":"","lastName":"Sun","suffix":""},{"id":317763910,"identity":"e725aacf-da27-4a4b-8f71-87eac49c3b55","order_by":7,"name":"Pengcheng Li","email":"","orcid":"","institution":"Zhongnan Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Pengcheng","middleName":"","lastName":"Li","suffix":""},{"id":317763911,"identity":"074bc020-0ae7-48bf-9961-7554cf737fca","order_by":8,"name":"Xiaodan Su","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Xiaodan","middleName":"","lastName":"Su","suffix":""},{"id":317763912,"identity":"b7c84bbd-ee02-47c9-af68-9876546726db","order_by":9,"name":"Zhaogang Teng","email":"","orcid":"","institution":"Nanjing University of Posts \u0026 Telecommunications","correspondingAuthor":false,"prefix":"","firstName":"Zhaogang","middleName":"","lastName":"Teng","suffix":""},{"id":317763913,"identity":"11c8eeef-bfb7-45ee-b8ac-1d87579a4877","order_by":10,"name":"Ying Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqklEQVRIiWNgGAWjYDACdsYGhg8QpgGRWpgZGxhnkKgFiHhI0mJwmLlN2ratLrGBvXmbBEPNHWK0MLZJ57axJTbwHCuTYDj2jFgt23gSGyRyzCQYGw4TqcVym0Rig/wbUrQwbjMA2sJDpBbJw4zNlr3/EozbeNKKLRKOEaGF73j7wxs/ztTJ9rMf3njjQw0RWhQOQBlsICKBsAYGBvkGYlSNglEwCkbByAYAo1M0se225f0AAAAASUVORK5CYII=","orcid":"","institution":"Wenzhou University of Technology","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-06-10 08:36:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4556757/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4556757/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10934-024-01668-8","type":"published","date":"2024-08-22T15:57:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59525867,"identity":"6b167ec3-0af4-4672-a6c6-a79de95b45be","added_by":"auto","created_at":"2024-07-02 20:57:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":212256,"visible":true,"origin":"","legend":"\u003cp\u003e(a, b) TEM images of the tHMONs-NH\u003csub\u003e2\u003c/sub\u003e; (c) TEM images and (d, e) SEM images of the CuS/tHMONs; (f) Lattice fringe image of the CuS nanoparticles within the CuS/tHMONs; (g) Hydrodynamic size distribution curves, (h) zeta potentials, and (i) FT-IR spectra of the CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/6c72e35a842cfd5e665129d4.png"},{"id":59524889,"identity":"eec26f50-f35a-4d92-9469-20eeac63df88","added_by":"auto","created_at":"2024-07-02 20:49:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":129851,"visible":true,"origin":"","legend":"\u003cp\u003e(a, b) XPS spectra of the CuS/tHMONs; (c) Nitrogen adsorption-desorption isotherms and corresponding (d) pore size distribution curves of the CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/4426333ad5de61fe4bdd07ce.png"},{"id":59524886,"identity":"f4e6cf8c-83ba-4850-b25e-7b9329575043","added_by":"auto","created_at":"2024-07-02 20:49:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":555524,"visible":true,"origin":"","legend":"\u003cp\u003e(a) HAADF image of the CuS/tHMONs; (b‒g) EDX elemental images of the CuS/tHMONs, orange, blue, aqua, green, yellow, and purple represent the six elements copper, sulfur, carbon, nitrogen, silicon, and oxygen, respectively; (h) Merged elemental image of the CuS/tHMONs.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/4ada698c87931b31dfa6c549.png"},{"id":59524883,"identity":"d49a1ed7-acc1-492a-bc95-83616ee389c7","added_by":"auto","created_at":"2024-07-02 20:49:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":307487,"visible":true,"origin":"","legend":"\u003cp\u003e(a) UV‒vis spectra of the CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e; (b) The heating curves of different concentrations of aqueous CuS/tHMON solutions after 5 min of irradiation with a near-infrared laser (power density: 1.25 W/cm\u003csup\u003e2\u003c/sup\u003e); (c) The heating curves of CuS/tHMON solution (concentration: 200 µg/mL) after 5 min of near-infrared laser irradiation with different power densities; (d) Photothermal stability curves of the CuS/tHMONs under five 808 nm laser irradiations; (e) Thermal imaging photographs of various concentrations of CuS/tHMON aqueous solutions after 5 min of near-infrared laser irradiation at a power density of 1.25 W/cm\u003csup\u003e2\u003c/sup\u003e; (f) Thermal imaging photographs of CuS/tHMONs solution (200 µg/mL) under various power densities for 5 min; (g) The photothermal heating curve of the 100 µg/mL CuS/tHMON under laser irradiation and cooling curve after turning off the laser; (h) The inset shows the linear relationship between -ln θ and time obtained from the cooling.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/51b4b58603901c8fe07a11a3.png"},{"id":59524885,"identity":"22b9759e-ecfd-4405-b25a-251bd675b442","added_by":"auto","created_at":"2024-07-02 20:49:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":134672,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Cell viability after incubation of 143B cells with different concentrations of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e for 24 h or 48 h; (b) Cell viability after incubation of 143B cells with different concentrations of CuS/tHMONs for 24 h or 48 h; Cell viability of 143B cells incubated with different concentrations of (c) tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and (d) CuS/tHMONs after applying an 808 nm laser (1.5 W/cm\u003csup\u003e2\u003c/sup\u003e) irradiation for 5 min.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/01b937ef747151138af8e9be.png"},{"id":63300599,"identity":"9ca5bc58-ff1a-4a7d-85cc-ea21db220508","added_by":"auto","created_at":"2024-08-26 16:15:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1902546,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/ebb6cdfd-7b7e-4db2-86c0-3b0aebb85183.pdf"},{"id":59524887,"identity":"fe02296a-1917-485f-a62b-bba1ddf19cf6","added_by":"auto","created_at":"2024-07-02 20:49:24","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":500249,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4556757/v1/6debfaeae7fae4f64db47259.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Facile synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMesoporous materials have attracted significant attention due to their remarkable characteristics, including high surface area, large pore volume, and uniform mesopores [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These materials serve as desirable matrices for constructing functional composites by incorporating metals and metal oxides, which hold great promise in catalysis, sensing, and biomedicine [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Synthesis of functional mesoporous composites with controlled morphologies and architectures is crucial for their practical applications [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMesoporous composites with different morphologies, including sphere [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], heterostructure [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and hollow structures [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] have been successfully synthesized. The structures offer the mesoporous composites with unique properties and potential applications in various fields. Notably, hollow materials have attracted increasing attention as platforms for preparation of advanced functional composites, thanks to their unique features such as large cavity and heterogeneous interfaces [\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For instance, Wu et al. achieved the integration of multi-shelled mesoporous silica nanoparticles with gold nanoparticles through electrostatic adsorption [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Li et al. reported enzyme-loaded multi-shelled metal-organic frameworks using an epitaxial shell-by-shell overgrowth method, which acted as nanoreactors to enhance catalytic efficiency in incompatible tandem biocatalytic processes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, the synthesis of multi-shelled mesoporous composites still faces challenges including poor product homogeneity and time-consuming procedures. In our previous work, we successfully prepared hollow mesoporous organosilica nanoparticles (HMONs) with multiple shells using a multi-interface transformation strategy [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Moreover, we hybridized HMONs with organic groups with coordination ability to metal ions by employing different organosilanes as precursors [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. These findings have inspired us to pursue the preparation of functional multi-shelled mesoporous composites.\u003c/p\u003e \u003cp\u003eHerein, we successfully prepared CuS nanoparticles loaded mesoporous organosilica nanospheres with triple-shelled hollow sturcture (CuS/tHMONs). The synthesis procedures involved the preparation of amino-hybridized triple-shelled hollow mesoporous organosilica nanoparticles through a multiple-interface transformation approach, followed by an \u003cem\u003ein situ\u003c/em\u003e growth of CuS nanoparticles on the mesoporouos shells. The resulting CuS/tHMONs exhibited a well-defined triple-shell hollow structure, uniform size (340 nm), and mesoporous channels with a diameter of 3.80 nm. In addition, the CuS/tHMONs exhibited excellent photothermal conversion efficiency (18.38%) and good photothermal stability under 808 nm laser irradiation. \u003cem\u003eIn vitro\u003c/em\u003e cytotoxicity assays revealed that the CuS/tHMONs possess excellent biocompatibility and excellent efficacy in photothermal therapy against human osteosarcoma 143B cells.\u003c/p\u003e"},{"header":"2. Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Materials\u003c/h2\u003e \u003cp\u003eCetyltrimethylammonium bromide (CTAB) (99 wt%), aqueous ammonia solution (25\u0026ndash;28 wt%), tetraethyl orthosilicate (TEOS), copper chloride dihydrate, hydrochloric acid, and anhydrous ethanol were obtained from Sinopharm Chemical Reagents Co., Ltd. (Shanghai, China). (3-Aminopropyl)triethoxysilane and 1,2-bis(triethoxysilyl)ethane (BTSE) were purchased from Sigma-Aldrich (Shanghai, China). Sodium sulfide nonahydrate and sodium citrate were obtained from Shanghai Macklin Biochemical Co., Ltd. (Shanghai, China). Minimum essential medium (MEM) and fetal bovine serum (FBS) were purchased from Grand Island Biological Company (NY, USA). Phosphate-buffered saline and Cell Counting Kit-8 were acquired from Lanjiike Technology Co., Ltd. (Hefei, China).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Synthesis\u003c/h2\u003e \u003cp\u003eThe synthesis of amino-hybridized triple-shelled hollow mesoporous organosilica nanoparticles (tHMONs-NH\u003csub\u003e2\u003c/sub\u003e) followed the typical procedure outlined below: First, 0.16 g of CTAB was dissolved in a mixed solution containing 1 mL of concentrated ammonia aqueous solution (25 wt%), 30 mL of ethanol, and 75 mL of water at 35\u0026deg;C. After 1 h, a mixture of APTES (0.625 mL), BTSE (0.0625 mL), and TEOS (0.125 mL) was rapidly added under vigorous stirring. The resulting mixture was stirred at 35\u0026deg;C for 24 h. Afterwards, the mesostructured hybridized nanospheres were collected by centrifugation at 10,000 rpm for 10 min and washed three times with ethanol. The obtained mesostructured nanospheres were then dispersed again in a mixed solution of CTAB (0.16 g), deionized water (75 mL), and ethanol (30 mL). After 30 min of ultrasonic dispersion, 1 mL of concentrated aqueous ammonia solution was added, and the mixture was placed in a 35\u0026deg;C water bath for 1 h. The same doses of TEOS, BTSE, and APTES used in the first step were added and stirred for an additional 24 h, resulting in two-layer mesostructured nanospheres. The same procedure and experimental conditions were repeated to obtain three-layer mesostructured hybridized nanospheres. The three-layer mesostructured nanospheres were then dispersed in 30 mL of water and transferred to a stainless-steel autoclave lined with Teflon. The autoclave was placed in an air flow electric oven set to 140\u0026deg;C for 5 h. The resulting product was collected by centrifugation and washed with ethanol. The CTAB in the product was extracted three times in a solution comprising 200 mL of ethanol and 400 \u0026micro;L of concentrated HCl (37%) for 12 h, and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e was obtained.\u003c/p\u003e \u003cp\u003eTo load CuS nanoparticles in the tHMONs-NH\u003csub\u003e2\u003c/sub\u003e, 5 mL of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e (0.7 mg/mL) was mixed with 2.5 mL of CuCl\u003csub\u003e2\u003c/sub\u003e\u0026middot;2H\u003csub\u003e2\u003c/sub\u003eO (20 mM). After shaking for 12 h, 2.5 mL of sodium citrate (13.6 mM) and 0.2 mL of Na\u003csub\u003e2\u003c/sub\u003eS\u0026middot;9H\u003csub\u003e2\u003c/sub\u003eO (0.25 mM) were added to the mixture and stirred at room temperature for 10 min (600 rpm). The mixed solution was further stirred at 80\u0026deg;C for 10 min and then immersed in an ice bath for 20 min. Finally, the resulting CuS/tHMONs were collected by centrifugation at 10,000 rpm for 10 min and washed with ethanol three times.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Photothermal performance\u003c/h2\u003e \u003cp\u003eFirst, CuS/tHMONs were dispersed in 200 \u0026micro;L of deionized water and irradiated with an 808 nm laser at a power density of 1.25 W/cm\u003csup\u003e2\u003c/sup\u003e for 5 min. Additionally, CuS/tHMONs dispersed in water were subjected to irradiation with an 808 nm laser at various power densities. For the photothermal stability test, 200 \u0026micro;L aqueous solution of CuS/tHMONs (200 \u0026micro;g/mL) was irradiated with a 1.25 W/cm\u003csup\u003e2\u003c/sup\u003e laser at 808 nm for 5 cycles. Each cycle consisted of a heating time of 3 min and a cooling time of 6 min. The temperature of the solution was recorded using an infrared camera from Fotric Company and Analyzir software. The photothermal conversion efficiency of CuS/tHMONs was calculated using the following formula:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\varvec{\\eta }=\\frac{hs\\left({T}_{max}-{T}_{amb}\\right)-{Q}_{0}}{I(1-{10}^{-A})}\\times 100\\%$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIn this formula, \u003cem\u003eh\u003c/em\u003e is the heat transfer coefficient, \u003cem\u003eS\u003c/em\u003e is the vessel surface area, \u003cem\u003eT\u003c/em\u003e\u003csub\u003e\u003cem\u003emax\u003c/em\u003e\u003c/sub\u003e is the maximum temperature under light radiation, \u003cem\u003eT\u003c/em\u003e\u003csub\u003e\u003cem\u003eamb\u003c/em\u003e\u003c/sub\u003e is the ambient temperature, \u003cem\u003eI\u003c/em\u003e is the laser power, A is the absorbance of the sample solution at 808 nm, and \u003cem\u003eQ\u003c/em\u003e\u003csub\u003e0\u003c/sub\u003e is the water and heat loss from light absorbed by the sample cell. \u003cem\u003ehS\u003c/em\u003e was calculated according to the following formula:\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$hS=\\frac{{m}_{D}{C}_{D}}{{\\tau }_{s}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003ewhere \u003cem\u003em\u003c/em\u003e\u003csub\u003e\u003cem\u003eD\u003c/em\u003e\u003c/sub\u003e and \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003eD\u003c/em\u003e\u003c/sub\u003e are the mass and heat capacity of deionized water (4.2 J/g), respectively, and \u003cem\u003eτ\u003c/em\u003e\u003csub\u003es\u003c/sub\u003e is the system time constant, calculated according to the following formula:\u003cdiv id=\"Equc\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e\n$$t={\\tau }_{s}In\\frac{T-{T}_{amb}}{{T}_{max}-{T}_{amb}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003ewhere \u003cem\u003et\u003c/em\u003e is the time value point of the cooling stage and \u003cem\u003eT\u003c/em\u003e is the real-time temperature corresponding to each time value point.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Cytotoxicity assay and photothermal therapy\u003c/h2\u003e \u003cp\u003eIn the cell viability assay, 143B osteosarcoma cells were seeded in 96-well plates at a density of 50,000 cells per well in 50 \u0026micro;L of MEM supplemented with 10% FBS. The plates were then placed in a 5% CO\u003csub\u003e2\u003c/sub\u003e incubator at 37\u0026deg;C (Thermo Fisher HERA cell 150i incubator). After 12 h of cell seeding, the medium was replaced with fresh medium containing different concentrations of the materials being tested. The concentrations used were as follows: CuS/tHMONs: 0, 10, 20, 30, 40, and 50 \u0026micro;g/mL; tHMONs-NH\u003csub\u003e2\u003c/sub\u003e: 0, 10, 20, 40, 80, and 160 \u0026micro;g/mL.\u003c/p\u003e \u003cp\u003eCell viability was assessed using a CCK8 assay. Specifically, 10 \u0026micro;L of CCK8 solution was added to each well at 24 h and 48 h after treatment. The plates were then incubated for a specified period, and the optical density (OD) at 450 nm was measured using a Multiskan FC-type plate reader from Thermo Fisher. The measurements were performed in triplicate for each sample (n\u0026thinsp;=\u0026thinsp;6).\u003c/p\u003e \u003cp\u003eFor the photothermal therapy assay, the same concentrations of CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e mixed media were placed in separate wells and incubated for 24 h. The cells were then subjected to irradiation under a power density of 1.5 W/cm\u003csup\u003e2\u003c/sup\u003e for 5 min. Following the treatment, cell cytotoxicity was assessed using the CCK8 assay.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Characterization\u003c/h2\u003e \u003cp\u003eTransmission electron microscopy (TEM) images were obtained at 100 kV on a Hitachi HT7700 microscope (Tokyo, Japan). High-resolution TEM (HR-TEM) images were captured using an FEI Talos F200x electron microscope (Hillsboro, USA). Scanning electron microscopy (SEM) images were captured using a Hitachi-S4800 microscope (Tokyo, Japan) at 5 kV and 10 mA. High-angle annular dark-field scanning electron microscopy (HAADF-STEM) and energy dispersive X-ray (EDX) images of the CuS/tHMONs were obtained on an FEI Talos F200X (Hillsboro, USA). The Fourier transform infrared (FT-IR) spectra were measured using a NEXUS870 infrared spectrometer (Madison, USA). The valence states of the copper and sulfur in CuS/tHMONs were tested using an Axis Supra X-ray photoelectron spectroscopy (XPS) from Kratos (Manchester, UK). Dynamic light scattering measurements were performed using a ZetaPLAS analyzer from Brookhaven (New York, USA). The nitrogen adsorption-desorption isotherms of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs were measured at -196 ℃ using a V-Sorb 2800P specific surface area analyzer. (Beijing, Chian). The pore size distribution was calculated using the Barret-Joyner-Halenda (BJH) method.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Synthesis and characterization\u003c/h2\u003e \u003cp\u003eTriple-shelled hollow mesoporous nanospheres hybridized with amino groups were first synthesized using a multiple-interface transformation approach [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. TEM images revealed that the prepared tHMONs-NH\u003csub\u003e2\u003c/sub\u003e has a uniform diameter of approximately 340 nm with three hollow chambers and a smooth surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, b). After loading CuS nanoparticles in situ, TEM images showed that the CuS/tHMONs maintained the triple-shell hollow structure and spherical shape (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). The surface of CuS/tHMONs appeared rougher due to the presence of tightly anchored CuS nanoparticles. Low-magnification SEM images indicated the uniform size and morphology of CuS/tHMONs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). High-magnification SEM images revealed a rough surface of CuS/tHMONs, attributed to a layer of nanoparticles firmly attached to the surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee). HR-TEM images further confirmed the successful loading of CuS within CuS/tHMONs, as evidenced by the lattice spacing of 0.33 nm corresponding to the interplanar spacing of CuS nanodots with hexagonal phase (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ef). The hydrodynamic diameters of the tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs were measured to be 344 nm and 352 nm, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eg). The zeta potentials of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs were measured to be 37.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 mV and \u0026minus;\u0026thinsp;16.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84 mV, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eh). These results demonstrate that CuS nanodots were effectively attached to the positively charged tHMONs-NH\u003csub\u003e2\u003c/sub\u003e, resulting in a change in surface charge. Overall, the characterization results provide evidence for the synthesis of triple-shell hollow mesoporous nanoparticles hybridized with amino groups (tHMONs-NH\u003csub\u003e2\u003c/sub\u003e) and subsequent successful loading of CuS nanoparticles to form CuS/tHMONs, with the CuS nanoparticles tightly anchored on the tHMONs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe components of CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e were analyzed using FT-IR spectroscopy. The FT-IR spectra of CuS/tHMONs and tHMONs-NH\u003csub\u003e2\u003c/sub\u003e exhibited characteristic peaks at 1414 cm\u003csup\u003e-1\u003c/sup\u003e indicative of the vibration of the C-H bond in the CH\u003csub\u003e2\u003c/sub\u003e-CH\u003csub\u003e2\u003c/sub\u003e group and peaks at 3445 cm\u003csup\u003e-1\u003c/sup\u003ecorresponding to the vibration of the N-H bond in the -NH\u003csub\u003e2\u003c/sub\u003e group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ei). These peaks confirmed the presence of the organosilica precursors APTES and BTSE in the products, indicating their successful condensation. XPS analysis of CuS/tHMONs revealed three signals at 931.6 eV, 283.4 eV, and 168.6 eV, corresponding to Cu, C, and S, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The XPS curve of Cu 2p showed characteristic peaks of Cu 2p1/2 and Cu 2p3/2 at 950.5 eV and 930.6 eV, respectively, confirming that the valence state of copper in CuS/tHMONs was +\u0026thinsp;2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The nitrogen adsorption-desorption isotherms of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs exhibited a type IV curve with a hysteresis loop, indicating a typical mesoporous structure (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). The pore size distribution, calculated using the BJH method, revealed an uniform mesopore size of approximately 3.8 nm for both tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). This indicates that the loading of CuS nanoparticles did not significantly affect the mesoporous structure or pore size of the nanoparticles. In summary, the FT-IR spectroscopy confirmed the presence of the organosilica precursors in tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs. The XPS analysis confirmed the presence of copper and sulfur in CuS/tHMONs, with copper in the +\u0026thinsp;2 valence state. The nitrogen adsorption-desorption isotherms and pore size distribution demonstrated the mesoporous nature of both tHMONs-NH\u003csub\u003e2\u003c/sub\u003e and CuS/tHMONs, with an uniform pore size of approximately 3.8 nm after the loading of CuS nanoparticles.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo investigate the distribution of CuS nanoparticles within the structure of CuS/tHMONs, HR-TEM and energy-dispersive X-ray spectroscopy (EDX) were employed. High-angle annular dark-field (HAADF) images revealed that the CuS/tHMONs maintained a well-defined triple-shell hollow structure, indicating that the \u003cem\u003ein situ\u003c/em\u003e synthesis of CuS did not disturb the hollow structure (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Elemental mapping images of CuS/tHMONs demonstrated the distribution of Cu, C, N, Si, O, and S elements within the three shells (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb‒g). To further analyze the spatial distribution of these elements, elemental line scan curves were performed for Cu, S, and Si (Fig. S2a). The Si signals were observed at 26 nm, 42 nm, and 82 nm, corresponding to the positions of the three shells in the range of 0 to 100 nm. The signals of both Cu and S were most prominent at 26 nm, indicating that the CuS nanoparticles were primarily adsorbed on the outermost shell layer (Fig. S2b). This observation is attributed to the fact that Cu\u003csup\u003e2+\u003c/sup\u003e at the outermost shell consumed a significant amount of S\u003csup\u003e2-\u003c/sup\u003e during the reaction, while a relatively small amount of S\u003csup\u003e2-\u003c/sup\u003e diffused into the cavity of tHMONs-NH\u003csub\u003e2\u003c/sub\u003e through the mesoporous channels. In summary, the HR-TEM and EDX analysis confirmed that CuS/tHMONs maintained a triple-shell hollow structure. The elemental mapping images provided visual evidence of the distribution of Cu, C, N, Si, O, and S elements within the three shells of the nanospheres.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Photothermal performance\u003c/h2\u003e \u003cp\u003eThe UV‒vis curve of CuS/tHMONs exhibited a broad peak at near-infrared wavelengths compared to tHMONs-NH\u003csub\u003e2\u003c/sub\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea). This indicates that CuS/tHMONs has enhanced light absorption in the near-infrared region. The photothermal effects of CuS/tHMONs under near-infrared (NIR) irradiation were studied by measuring the temperature profiles of CuS/tHMONs at various concentrations (0‒300 \u0026micro;g/mL) under laser irradiation (808 nm, 1.25 W/cm\u003csup\u003e2\u003c/sup\u003e). The results showed that CuS/tHMONs increase the temperature from 25\u0026deg;C to 45\u0026deg;C at a concentration of 300 \u0026micro;g/mL, and the temperature profiles displayed a concentration-dependent behavior (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb). In contrast, water exhibited negligible temperature change (\u0026lt;\u0026thinsp;3\u0026deg;C) under the same conditions. Additionally, the heating curve of CuS/tHMONs exposed to different laser powers demonstrated a positive correlation between temperature and laser power density (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec). The photothermal stability of CuS/tHMONs was evaluated by subjecting the nanospheres to five successive irradiation-heating and natural cooling cycles (cycle time: 180 s). The photothermal stability curve showed no significant reduction in temperature after each cycle, indicating excellent photothermal stability (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed). Thermal images of CuS/tHMONs further confirmed the time and concentration-dependent photothermal conversion of the nanospheres (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee‒f). The system time constant (τs) was determined to be 238 s by analyzing the linear regression curve between the cooling stage of CuS/tHMONs and the negative natural logarithm of the driving force temperature. Based on this analysis, the photothermal conversion efficiency of CuS/tHMONs was calculated to be approximately 18.38% (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eg‒h), indicating their efficient photothermal conversion property. In summary, the UV‒vis analysis revealed enhanced light absorption in the near-infrared region for CuS/tHMONs. The nanospheres exhibited excellent photothermal stability, maintaining their temperature increase after multiple irradiation-heating cycles. The photothermal effects of CuS/tHMONs were concentration-dependent, with significant temperature elevation under NIR irradiation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Cytotoxicity assay and photothermal property\u003c/h2\u003e \u003cp\u003eTo assess the potential biological applications of CuS/tHMONs, the cytotoxicity and photothermal therapy effects of the nanocomposites were evaluated in 143B osteosarcoma cells. The cytotoxicity assay demonstrated that cell viability remained above 80% when the cells were incubated with tHMONs-NH\u003csub\u003e2\u003c/sub\u003e or CuS/tHMONs for 24 or 48 h, indicating good biocompatibility of the triple-shell mesoporous nanospheres (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea, b). Under laser irradiation, the cell viability of 143B cells incubated with tHMONs-NH\u003csub\u003e2\u003c/sub\u003e remained above 80% (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). In contrast, the viability of 143B cells incubated with CuS/tHMONs exhibited a clear concentration-dependent response (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed). At a concentration of 50 \u0026micro;g/mL of CuS/tHMONs, only approximately 40% of the cells survived, indicating the excellent photothermal therapy effect of CuS/tHMONs. In summary, the cytotoxicity assay demonstrated the good biocompatibility of CuS/tHMONs, with cell viability above 80% after incubation. However, under laser irradiation, the photothermal therapy effect of CuS/tHMONs was evident, indicating the potential of CuS/tHMONs for effective photothermal therapy in 143B osteosarcoma cells.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn conclusion, the synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure (CuS/tHMONs) was successfully achieved. These nanocomposites exhibited a spherical shape, triple-shell structure, uniform size (340 nm), and well-defined mesoporous channels (3.80 nm). HAADF images and element mapping confirmed the presence of a significant amount of CuS loaded within the frameworks. The photothermal conversion efficiency of CuS/tHMONs was calculated to be 18.38%, indicating their efficient conversion of light into heat. Photothermal experiments demonstrated that CuS/tHMONs possessed excellent photothermal stability. Furthermore, cell viability analysis revealed that the CuS/tHMONs exhibited good biocompatibility in the absence of laser irradiation. When subjected to 808 nm laser irradiation, CuS/tHMONs exhibited a notable inhibitory effect against human osteosarcoma 143B cells, indicating their potential for tumor photothermal treatment. In summary, the synthesized CuS/tHMONs composite nanospheres displayed a well-defined structure, efficient photothermal conversion, excellent photothermal stability, good biocompatibility, and demonstrated a promising inhibitory effect on osteosarcoma cells under laser irradiation. These findings highlight the preparation of mesoporous composites with mutil-shelled hollow structures and the potential for applications in tumor photothermal therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eXuzhi Shi:\u003c/strong\u003e Writing\u0026ndash;original draft. \u003cstrong\u003eYifeng Yu:\u003c/strong\u003e Biological experiments. \u003cstrong\u003eRuifa Yu:\u003c/strong\u003e Materials synthesis. \u003cstrong\u003eNing Wang:\u003c/strong\u003e Writing\u0026ndash;original draft. \u003cstrong\u003eWei Lu:\u003c/strong\u003e Biological experiments, Writing\u0026ndash;original draft. \u003cstrong\u003eXiaolin Han:\u003c/strong\u003e Materials synthesis. \u003cstrong\u003eTangyao Sun:\u003c/strong\u003e Materials synthesis. \u003cstrong\u003ePengcheng Li:\u003c/strong\u003e Conceptualization, Writing\u0026ndash;review and editing. \u003cstrong\u003eXiaodan Su:\u003c/strong\u003e Characterization. \u003cstrong\u003eZhaogang Teng:\u003c/strong\u003e Writing\u0026ndash;review and editing. \u003cstrong\u003eYing Liu:\u003c/strong\u003e Writing\u0026ndash;review and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (81971675, 21603106), Natural Science Foundation of Hubei Province(2022CFB973), Program for Science and Technology Development of Wenzhou (Y20210226) and Scientific Research Fund of Zhejiang Provincial Education Department (Y202250265). X.S. and Y.Y. authors contributed equally to this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Competing Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo data was used for the research described in the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eT.C. Zhao, A. Elzatahry, X.M. Li, D.Y. Zhao, Single-micelle-directed synthesis of mesoporous materials. Nat. Rev. Mater. 4, 775-791 (2019). https://doi.org/10.1038/s41578-019-0144-x\u003c/li\u003e\n\u003cli\u003eS.L. Suib, A review of recent developments of mesoporous materials. Chem. Rec. 17(12), 1169-1183 (2017). https://doi.org/10.1002/tcr.201700025\u003c/li\u003e\n\u003cli\u003eW. Zhang, Y. Tian, H.L. He, L. Xu, W. Li, D.Y. Zhao, Recent advances in the synthesis of hierarchically mesoporous TiO2 materials for energy and environmental applications. Natl. Sci. Rev. 7 (11), 1702-1725 (2020). https://doi.org/10.1093/nsr/nwaa021\u003c/li\u003e\n\u003cli\u003eL.H. Zu, W. Zhang, L.B. Qu, L.L. Liu, W. Li, A. Yu, D.Y. Zhao, Mesoporous materials for electrochemical energy storage and conversion. Adv. Energy Mater. 10 38), 2002152 (2020). https://doi.org/10.1002/aenm.202002152\u003c/li\u003e\n\u003cli\u003eL.L. Duan, C.Y. Wang, W. Zhang, B. Ma, Y.H. Deng, W. Li, D.Y. Zhao, Interfacial assembly and applications of functional mesoporous materials. Chem. Rev. 121 (23), 14349-14429 (2021). https://doi.org/10.1021/acs.chemrev.1c00236\u003c/li\u003e\n\u003cli\u003eW. Li, J. Liu, D.Y. Zhao, Mesoporous materials for energy conversion and storage devices. Nat. Rev. Mater. 1 (6), 1-17 (2016). https://doi.org/10.1038/natrevmats.2016.23\u003c/li\u003e\n\u003cli\u003eJ.Z. Yao, N.R. Sun, C.H. Deng, Recent advances in mesoporous materials for sample preparation in proteomics research. Trends Anal. Chem. 99, 88-100 (2018). https://doi.org/10.1016/j.trac.2017.11.016\u003c/li\u003e\n\u003cli\u003eP.P. Qiu, B. Ma, C.T. Hung, W. Li, D.Y. Zhao, Spherical mesoporous materials from single to multilevel architectures. Acc. Chem. Res. 52 (10), 2928-2938 (2019).\u003c/li\u003e\n\u003cli\u003eR.K. Kankala, H.B. Zhang, C.G. Liu, K.R. Kanubaddi, C.H. Lee, S.B. Wang, W.G. Cui, H. A. Santos, K.L. Lin, A.Z. Chen, Metal species-encapsulated mesoporous silica nanoparticles, current advancements and latest breakthroughs. Adv. Funct. Mater. 29 (2019), 1902652 (2019). https://doi.org/10.1021/acs.accounts.9b00357\u003c/li\u003e\n\u003cli\u003eH. Liu, Y. Feng, D. Chen, C.Y. Li, P.L. Cui, J. Yang, Noble metal-based composite nanomaterials fabricated via solution-based approaches. J. Mater. Chem. A. 3 (7), 3182-3223 (2015). https://doi.org/10.1039/C4TA05801A\u003c/li\u003e\n\u003cli\u003eP. Karami, S.S. Khasraghi, M. Hashemi, S. Rabiei, A. Shojaei, Polymer/nanodiamond composites-a comprehensive review from synthesis and fabrication to properties and applications. Adv. Colloid Interface Sci. 269, 122-151 (2019). https://doi.org/10.1016/j.cis.2019.04.006\u003c/li\u003e\n\u003cli\u003eZ.H. Zhang, C.H. Liu, J.H. Bai, C.C. Wu, Y. Xiao, Y.H. Li, J. Zheng, R.H. Yang, W.H. Tan, Silver nanoparticle gated, mesoporous silica coated gold nanorods (AuNR@MS@AgNPs), low premature release and multifunctional cancer theranostic platform. ACS Appl. Mater. Interfaces. 7 (11), 6211-6219 (2015). https://doi.org/10.1021/acsami.5b00368\u003c/li\u003e\n\u003cli\u003eH.B. Zou, J.Y. Dai, J.Q Suo, R. Ettelaie, Y. Li, N. Xue, R.W. Wang, H.Q. Yang, Dual metal nanoparticles within multicompartmentalized mesoporous organosilicas for efficient sequential hydrogenation. Nat. Commun. 12 (1), 1-11 (2021). https://doi.org/10.1038/s41467-021-25226-x\u003c/li\u003e\n\u003cli\u003eW.N. Zeng, D. Wang, Q.P. Yu, Z.P. Yu, H.Y. Wang, C.Y. Wu, S.W. Du, X.Y. Chen, J.F. Li, Z.K. Zhou, Y. Zeng, Y. Zhang, Near-infrared light-controllable multifunction mesoporous polydopamine nanocomposites for promoting infected wound healing. ACS Appl. Mater. Interfaces. 14 (2), 2534-2550 (2022). https://doi.org/10.1021/acsami.1c19209\u003c/li\u003e\n\u003cli\u003eM.L. Liu, L. Chen, Z.W. Zhao, M.C. Liu, T.C. Zhao, Y.Z. Ma, Q.Y. Zhou, Y. S. Ibrahim, A. A. Elzatahry, X.M. Li, D.Y. Zhao, Enzyme-based mesoporous nanomotors with near-infrared optical brakes. J. Am. Chem. Soc. 144 (9), 3892-3901 (2022). https://doi.org/10.1021/jacs.1c11749\u003c/li\u003e\n\u003cli\u003eY.X. Ji, X.K. Lin, H.Y. Zhang, Y.J. Wu, J.B. Li, Q. He, Thermoresponsive polymer brush modulation on the direction of motion of phoretically driven janus micromotors. Angew. Chem. Int. Ed. 58 (13), 4184-4188 (2019). https://doi.org/10.1002/anie.201812860\u003c/li\u003e\n\u003cli\u003eY. Xing, M.Y. Zhou, T.L. Xu, S.S. Tang, Y. Fu, X. Du, L. Su, Yongqiang Wen, Xueji Zhang, Tianyi Ma, Core@satellite Janus nanomotors with pH‐responsive multi‐phoretic propulsion. Angew. Chem. Int. Ed. 59 (34), 14368-14372 (2020). https://doi.org/10.1002/anie.202006421\u003c/li\u003e\n\u003cli\u003eH.J. Wang, J. Tao, C.L. Xu, Y. Tian, G.M. Lu, B. Yang, Z.G. Teng, Flexible CuS-embedded human serum albumin hollow nanocapsules with peroxidase-like activity for synergistic sonodynamic and photothermal cancer therapy. Nanoscale, 14 (27), 9702-9714 (2022).\u003c/li\u003e\n\u003cli\u003eP. Xu, Z.G. Wu, W.Dai, Y. Wang, M.K. Zheng, X.D. Su, Z.G. Teng, Synthesis of multiple Ag nanoparticles loaded hollow mesoporous carbon spheres for highly efficient and recyclable catalysis. Microporous Mesoporous Mater. 314, 110856 (2021). https://doi.org/10.1016/j.micromeso.2020.110856\u003c/li\u003e\n\u003cli\u003eN. Lu, W.P. Fan, X. Yi, S. Wang, Z.T. Wang, R. Tian, O. Jacobson, Y.J. Liu, B.C. Yung, G.F. Zhang, Z.G. Teng, K. Yang, M.M. Zhang, G. Niu, G.G. Lu, X.Y. Chen, Biodegradable hollow mesoporous organosilica nanotheranostics for mild hyperthermia-induced bubble-enhanced oxygen-sensitized radiotherapy. ACS Nano. 12 (2), 1580-1591 (2018). https://doi.org/10.1021/acsnano.7b08103\u003c/li\u003e\n\u003cli\u003eJ.Y. Wang, H.J. Tang, H. Wang, R.B. Yu, D. Wang, Multi-shelled hollow micro-/nanostructures, promising platforms for lithium-ion batteries. Mater. Chem. Front. 1 (3), 414-430 (2017). https://doi.org/10.1039/C6QM00273K\u003c/li\u003e\n\u003cli\u003eX.J. Wang, J. Feng, Y.C. Ba, Q. Zhang, Y.D. Yin, Synthesis, properties, and applications of hollow micro-/nanostructures. Chemical Reviews. 116 (18), 10983-11060 (2016). https://doi.org/10.1021/acs.chemrev.5b00731\u003c/li\u003e\n\u003cli\u003eWang J, Wan J, Yang N, et al. Hollow multishell structures exercise temporal\u0026ndash;spatial ordering and dynamic smart behaviour. Nat. Rev. Chem. 4(3), 159-168 (2020). https://doi.org/10.1038/s41570-020-0161-8\u003c/li\u003e\n\u003cli\u003eJ.Y. Wang, J.W. Wan, N.L. Yang, Q. Li, D. Wang, A versatile ligand-assisted cooperative template method to synthesize multi-shelled mesoporous hollow metal hydroxide and oxide nanospheres as catalytic reactors. Nano Res. 14, 3260-3266 (2021). https://doi.org/10.1007/s12274-021-3403-2\u003c/li\u003e\n\u003cli\u003eR. Amal, Promising hollow multi-shelled structures, discovering the temporal-spatial ordering. Natl. Sci. Rev. 7 (11), 1763-1764 (2020). https://doi.org/10.1093/nsr/nwaa106\u003c/li\u003e\n\u003cli\u003eL. Wu, H.J. Zhang, M.H. Wu, Y.F. Zhong, X.W. Liu, Z. Jiao, Dual-templating synthesis of multi-shelled mesoporous silica nanoparticles as catalyst and drug carrier. Microporous Mesoporous Mater. 228 (1), 318-328 (2016). https://doi.org/10.1016/j.micromeso.2016.03.040\u003c/li\u003e\n\u003cli\u003eT.T. Man, C.X. Xu, X.Y. Liu, D. Li, C.K. Tsung, H. Pei, Y. Wan, L. Li, Hierarchically encapsulating enzymes with multi-shelled metal-organic frameworks for tandem biocatalytic reactions. Nat. Commun. 13 (1), 1-12 (2022). https://doi.org/10.1038/s41467-022-27983-9\u003c/li\u003e\n\u003cli\u003eZ.G. Teng, X.D. Su, Y.Y. Zheng, J.J. Zhang, Y. Liu, S.J. Wang, J. Wu, G.T. Chen, J.D. Wang, D.Y. Zhao, G.G. Lu, A facile multi-interface transformation approach to monodisperse multiple-shelled periodic mesoporous organosilica hollow spheres. J. Am. Chem. Soc. 137 (24), 7935-7944 (2015). https://doi.org/10.1021/jacs.5b05369\u003c/li\u003e\n\u003cli\u003eR.F. Yu, J. Tao, L.X. Shao, W. Lu, J.J Zhao, R. Tang, J. Li, Z.G. Teng, Facile synthesis of hybridized triple-shelled hollow mesoporous organosilica nanoparticles. J. Taiwan Inst. Chem. Eng. 131, 104122 (2022). https://doi.org/10.1016/j.jtice.2021.10.022\u003c/li\u003e\n\u003cli\u003eZ.G. Teng, J.J. Zhang, W. Li, Y.Y. Zheng, X.D. Su, Y.X. Tang, M. Dang, Y. Tian, L.H. Yuwen, L.X Weng, G.M Lu, L.H Wang, Facile synthesis of yolk-shell‐structured triple‐hybridized periodic mesoporous organosilica nanoparticles for biomedicine. Small 12 (26), 3550-3558 (2016). https://doi.org/10.1002/smll.201600616\u003c/li\u003e\n\u003c/ol\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":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-porous-materials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jopo","sideBox":"Learn more about [Journal of Porous Materials](http://link.springer.com/journal/10934)","snPcode":"10934","submissionUrl":"https://submission.nature.com/new-submission/10934/3","title":"Journal of Porous Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"mesoporous organosilica, composite nanospheres, hollow structure, triple-shell, photothermal","lastPublishedDoi":"10.21203/rs.3.rs-4556757/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4556757/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHerein, copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure (CuS/tHMONs) are successfully synthesized. The resulting CuS/tHMONs nanospheres exhibit a uniform diameter of 340 nm, mesoporous channels with a diameter of 3.8 nm, large pore volume, and triply separated cavities. High-angle annular dark-field scanning electron microscopy (HAADF-STEM) images confirm the presence of a high content of CuS nanoparticles within the CuS/tHMONs composite nanospheres. Moreover, the CuS/tHMONs nanospheres demonstrate high photothermal conversion efficiency and excellent photothermal stability. \u003cem\u003eIn vitro\u003c/em\u003e experiments reveal excellent biocompatibility of the CuS/tHMON nanospheres, and cytotoxic assays demonstrate their effectiveness in killing cancer cells through photothermal therapy.\u003c/p\u003e","manuscriptTitle":"Facile synthesis of copper sulfide loaded mesoporous organosilica nanospheres with a triple-shelled hollow structure","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-02 20:49:18","doi":"10.21203/rs.3.rs-4556757/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-07T21:19:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-29T10:21:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-22T04:31:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"64195952662922502353901146679754509698","date":"2024-06-21T07:17:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126834159123918985631732418530908833684","date":"2024-06-15T12:43:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"207334491819163764646314813820784713652","date":"2024-06-14T02:48:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"233204532268752483528371549700843903217","date":"2024-06-14T00:25:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-13T21:22:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-11T13:10:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-11T13:10:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Porous Materials","date":"2024-06-10T08:34:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-porous-materials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jopo","sideBox":"Learn more about [Journal of Porous Materials](http://link.springer.com/journal/10934)","snPcode":"10934","submissionUrl":"https://submission.nature.com/new-submission/10934/3","title":"Journal of Porous Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e634fafc-4ed4-4a77-8827-6694f95cde59","owner":[],"postedDate":"July 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T16:08:31+00:00","versionOfRecord":{"articleIdentity":"rs-4556757","link":"https://doi.org/10.1007/s10934-024-01668-8","journal":{"identity":"journal-of-porous-materials","isVorOnly":false,"title":"Journal of Porous Materials"},"publishedOn":"2024-08-22 15:57:22","publishedOnDateReadable":"August 22nd, 2024"},"versionCreatedAt":"2024-07-02 20:49:18","video":"","vorDoi":"10.1007/s10934-024-01668-8","vorDoiUrl":"https://doi.org/10.1007/s10934-024-01668-8","workflowStages":[]},"version":"v1","identity":"rs-4556757","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4556757","identity":"rs-4556757","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}