SWCNTs functionalized with gold nanoradiosensitizers as radiosensitizers for enhanced radiotherapy in breast cancer

SWCNTs functionalized with gold nanoradiosensitizers as radiosensitizers for enhanced radiotherapy in breast cancer | 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 Article SWCNTs functionalized with gold nanoradiosensitizers as radiosensitizers for enhanced radiotherapy in breast cancer Ali Mohammadi, Negin Hashemi, Zahra Asghariha, Marzieh Sadat Hosseini, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5354865/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Breast cancer is the most common and significant threat affecting women globally. Traditional methods have been widely used in cancer treatment for many years. However, the unavoidable side effects of these approaches are undeniable. Nanotechnology and carbon nanotubes offer the potential to improve traditional cancer treatments by reducing side effects and enhancing efficacy. In this project, we investigated the potential of Single-Walled Carbon Nanotubes (SWCNTs) as advanced delivery systems for chemotherapy agents directly within tumors, as well as their role as substrates for developing radiation sensitizers to enhance the efficacy of radiation therapy alone. To confirm the successful formation of the nanoparticles, we conducted various techniques such as Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), UV-Visible spectroscopy and X-Ray Diffraction (XRD) to ensure accurate verification. To evaluate the cytotoxicity of SWCNTs -Au-CUR nanoparticles, we performed MTT and hemolysis assays. Subsequently, we assessed the effectiveness of the synthesized nanoparticles at different concentrations, with and without the aid of X-ray, against cancer cells. Observed results showed the correct creation and high efficacy of these nanoparticles on cancerous cells. It also showed that the presence of X-rays amplified nanoparticle toxicity, increased the ROS levels in the cancerous cells, and resulted in more effective induction of DNA damage. Biological sciences/Cancer Biological sciences/Cell biology Physical sciences/Chemistry Physical sciences/Materials science Breast cancer Chemotherapy Radiation sensitizers Single-wall carbon nanotubes Curcumin Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Cancer has been recognized as a complex disease that poses a serious threat to human life [1]. Breast cancer is the most prevalent type of malignancy among women [2]. Various treatment options and medications have been utilized to combat this intense disease including surgery, radiotherapy and chemotherapy, each presenting its own set of challenges and limitations [3–6]. Radiation therapy, as a conventional treatment method has the potential to cause unfavorable side effects on surrounding healthy tissues. Chemotherapy is a widely employed approach for managing cancer, Involving the administration of single or multiple drugs. Unfortunately, this method also has drawbacks such as multidrug resistance (MDR), poor pharmacokinetic profile of anticancer drugs and a detrimental impact on normal cells [7]. To ameliorate the effectiveness of these traditional therapeutic approaches, utilizing radiation sensitizers such as carbon nanotubes and gold nanoparticles is recommended. Enhancing the absorption of radiation by cancer cells while minimizing the impact on non-cancerous cells is one of the most important advantages of these therapeutic approaches [8]. In contrast, these nanotubes possess the potential to act as carriers for delivering anti-cancer drugs to cancerous cells in a manner that leads fewer negative side effects compared to treatment with chemotherapy as a monotherapy [9, 10]. This novel approach demonstrates promise in the management of these issues [11]. In this study, curcumin has been Investigated as a candidate for anticancer drugs that exhibit poor pharmacokinetic properties. Curcumin is an active ingredient of the turmeric plant that possesses various effects, such as: antioxidant, anti-inflammatory and anticancer effects [12–14]. Curcumin impacts cancer cells through over 100 molecular pathways, including the downregulation of receptors such as HER-2, modulation of enzymes like COX-2 and ATPase, regulation of transcription factors like NF-kB and regulation of inflammatory cytokines such as IL-1 and IL-2 [15]. Furthermore, curcumin increases tumor sensitivity to medication and promotes cell death.[16]. Recent advancements in nanotechnology and these innovative techniques such as CNT-Au have shown potential for achieving greater efficacy with fewer side effects in cancer treatment. Sumio Iijima discovered multi-walled carbon nanotubes (MWCNTs) using electron microscopy in 1991. Subsequently, in 1993, Bethune discovered single-walled carbon nanotubes (SWCNTs) [17, 18]. Carbon nanotubes serve as carriers for delivering anticancer drugs, enhancing the specificity of treatment and improving the pharmacokinetic properties of these drugs, such as dissolution and stability [1, 19]. Gold nanoparticles, as radiation sensitizers, play a vital role in this treatment approach by reducing the dosage administered to non-cancerous cells. Moreover, these nanoparticles aid in the degradation of cancer cell DNA and enhance the treatment process through apoptosis induction [20]. Therefore, the objective of this study is to create gold nanoparticles and nanotubes for use as radiation sensitizers, intending to utilize them as a delivery system for curcumin in a combined chemotherapy and radiation therapy approach that leverages the strengths and mitigates the weaknesses of each treatment modality. This study will primarily assess response rates and evaluate the benefits and harms of this strategy. Method and Materials Materials MTT was acquired from Sigma Aldrich, a leading chemical supplier in the United States, Curcumin and dialysis bags were purchased from Merck KGaA, a global pharmaceutical and chemical company based in Darmstadt (Germany), The HFF-2 and the 4T1 were procured from the Pasteur Institute of Iran, a renowned research institution in the Middle East, Ethanol was procured from Kimia alcohol, a domestic supplier in Iran. Growth medium was acquired from Gibco, a leading life science technology company based in Germany. Methods SWCNT synthesis For the synthesis and purification of SWCNTs functionalized with Fe–Mo catalyst, we adopted a methodology previously reported [21]. Synthesis of SWCNTs functionalized with gold nanoparticles Gold nanoparticles were synthesized on a SWCNTs substrate by adding 0.9 mL of 1% sodium citrate solution and 1.036 mL of 0.45% HAuCL4 solution dropwise to a solution containing 4.7 mg of oxidized SWCNTs. A drop of 0.21 mg/mL NaBH4 solution was then added to the reaction mixture, which was stirred for 12 hours at 25°C. The formation of gold nanoparticles was indicated by a change in solution color to cherry. The solution was purified by dialysis for 48 hours. Curcumin-loaded SWCNTs -Au Curcumin(CUR) (4 mg) was dissolved in 1.25 mL of acetone and added dropwise to a suspension of 20 mg of SWCNTs-Au in water. The result compound was stirred at 25°C for 24 hours, then heated and centrifuged to remove any unbound CUR. Discovering the structure, physical and chemical properties Transmission Electron Microscopy (TEM) This technique enables the direct observation of nanoparticle morphology and size, as well as an understanding of their distribution and the degree of particle accumulation. Sample preparation involves first creating a dilute solution of nanoparticles in isopropyl alcohol or water. The resulting liquid was then dispersed and dried onto a carbon-coated grid. The analysis was then conducted using a TEM (Cambridge 360–1990 Stereo Scan Instrument, EDS, CA). UV-Vis analysis UV-Vis was used to analyze the quantitative properties of synthesized SWCNTs -Au, CUR, and SWCNTs -Au-CUR. Measurements were taken using a GENESYS10S spectrophotometer (Thermo Fisher Scientific, Madison, Wisconsin) over a wavelength range of 200–600 nm. FTIR analysis FTIR spectroscopy was used to detect polar functional groups in the synthesized materials. A Tensor 27 FT-IR spectrometer (Bruker, Biotage, Germany) was used to measure the infrared absorption spectra over a wavenumber range of 4000 − 400 \(\:{cm}^{-1}\) . XRD analysis XRD analysis of SWCNTs was performed using a D8-advance diffractometer (Bruker AXS) with Cu-Kα radiation (λ = 1.542 Å). The XRD data were collected over a 2θ range of 5 to 80 degrees. Drug Loading To load curcumin onto the primary nanocarrier system, 1 mg of SWCNTs -Au-CUR was dispersed in 2 mL of ethanol and incubated at 37°C for 24 hours. The mixture was then centrifuged at 5,000 rpm for 10 minutes to remove the supernatant. CUR Release Study The drug release profile was examined under two buffer conditions: physiological pH (7.4) and a tumor tissue simulator (pH 4.7). 1 mL of the synthetic SWCNTs -Au-CUR (containing 4 mg) was placed in a dialysis bag with a molecular weight cutoff of 12 kDa. The bag was then placed in 25 mL of a phosphate-ethanol buffer and placed in a shaking incubator at 100 rpm and 37°C. These procedures were conducted for both pH conditions with three repetitions. At predetermined time intervals, 1 mL of the solution was withdrawn from the outer chamber. The light absorption of the sample was measured at a wavelength of 430 nm using a UV-Vis spectrophotometer, and the sample was subsequently returned to the reaction container. Biocompatibility assessment The biocompatibility of the synthesized SWCNTs -Au was assessed in vitro using hemolysis and cytotoxicity tests on a healthy cell line. hemolysis The hemolysis test assesses the compatibility of nanoparticles with blood. This test involves mixing red blood cells with various concentrations of the prepared SWCNTs -Au, followed by a 4-hour incubation period at 37°C with gentle shaking. The absorbance of the supernatant at 540 nm was measured after deionized water (positive control) and PBS solution (negative control) were used to incubate the samples. The samples were then centrifuged at 1300 rpm for 15 minutes. Each concentration was evaluated in triplicate, and the percentage of hemolysis for each sample was calculated. Assessment of Cytotoxic Effects on non-cancerous Cells The cytotoxicity effects of the synthesized SWCNTs -Au on the HFF-2 cell line was evaluated using the MTT assay. Healthy Cells were treated with various concentrations of the SWCNTs -Au, with each concentration being tested in five replicates. In vitro therapeutic effects 4T1 cells (7,000 cells/well) were plated in 96-well plates and then incubated with various concentrations of nanoparticles for 4 hours. After washing with PBS, selected groups were exposed to X-rays at a dose of 6 Gy. All cells were then incubated for an additional 12 hours, and cell viability was assessed using the MTT test. Results Synthesis of CUR loaded SWCNTs-Au nanoparticles We synthesized and functionalized SWCNTs with gold nanoparticles in this study. Subsequently, the developed SWCNTs -Au was loaded with CUR. Morphological assessment TEM TEM imaging was used to characterize CWNTs-Au-CUR nanoparticles. This technique utilizes high-energy electrons to interact with the nanoparticles, allowing for the detailed examination of structures at the nanometer scale. Figure 1 presents the TEM images of the SWCNTs-Au-CUR nanoparticles. The images clearly show the formation of spherical nanoparticles supported by the single-walled carbon nanotube substrate. UV-Vis The UV-Vis spectrum showed characteristic peaks for curcumin at 430 nm, SWCNT-Au at 245 nm, and SWCNT-Au-CUR at 232–245 nm. The presence of both CUR and SWCNT-Au peaks in the SWCNT-Au-CUR spectrum confirmed the successful loading of CUR into the SWCNTs -Au. FTIR Figure 3 presents the FTIR analysis of the SWCNTs-Au-CUR nanoparticles FTIR analysis revealed characteristic peaks corresponding to O-H stretching vibrations (3450 cm − 1 ), aromatic C = C stretching vibrations (1581 − 1423 cm − 1 ), and Al2O3 vibrational modes (1640 cm − 1 ), consistent with previous studies [21]. Furthermore, peaks at 521 and 649 \(\:{cm}^{-1}\) , indicative of gold nanoparticles encapsulated with CUR via carbon nanotube coating, were noted; however, these peaks were absent in the final product. XRD The XRD pattern of the nanoparticles, presented in Fig. 4 , aligns with the standard XRD profiles for Au and SWCNTs. This is consistent with our previous study on SWCNTs. Drug-Loading The drug loading efficiency was determined to be 14.27% curcumin. $$\:drug\:loading\:content\left(\%\right)=\frac{weight\:of\:the\:drug\:in\:nanoparticles}{weight\:of\:the\:nanoparticles\:with\:drug}\times\:100$$ Drug release study The release kinetics of curcumin have been studied in two PBS-ethanol buffer systems with pH values of 7.4 and 4.7. As shown in Fig. 5 , curcumin release from the nanoparticles is relatively slow in both environments, with the highest release occurring in the acidic buffer. After 24 hours, about 39% of CUR was released in the neutral pH buffer, while the acidic environment resulted in approximately 56% release during the same period. These results indicate a pH-dependent release mechanism, where acidic conditions enhance CUR release. The differences in release can be attributed to two key factors: the solubility of CUR in the buffer and the environmental condition’s ability to disrupt interactions between CUR and the nanoparticle carrier. Thus, the extent of drug release is primarily influenced by the ability of the environmental parameters to weaken the binding interactions between the drug and the SWCNTs. Hemolysis In our biocompatibility study, we assessed the hematotoxicity of the synthesized SWCNTs (Fig. 6 ). Various concentrations of the SWCNTs were formulated with corresponding amounts of curcumin in each. The results showed that the SWCNTs had a dose-dependent response up to 200 µg/mL. Notably, the toxicity observed was less than 5%, indicating that the SWCNTs is safe for use. Cytotoxicity evaluation in HFF-2 cells We investigated the toxicity of nanoparticles on non-cancerous embryonic fibroblast cells using the MTT assay (Fig. 7 ). Our results showed that the toxicity of SWCNT-Au nanoparticles increases with higher concentrations. Specifically, exposure of HFF-2 cells with varying nanoparticle concentrations revealed a direct relationship between SWCNT-Au concentration and cytotoxicity. The control group exhibited no important differences when subjected to curcumin at various concentrations of 4, 15, and 20 µg/mL. This lack of effect may be due to curcumin's low efficacy as an anticancer agent, its limited solubility, or its inadequate cellular penetration. However, the results suggest that CUR does not cause toxicity in HFF-2 cells at concentrations of 20 µg/mL or lower. Therapeutic Effects on 4T1 Cells: With and Without X-Ray Radiation In this study, we evaluated cell viability at nanoparticle concentrations of 25 µg/mL, 75 µg/mL, and 100 µg/mL, alongside X-ray irradiation at a dose of 6 Gy (Fig. 8 ). The anticancer effectiveness of the developed SWCNTs was assessed using the 4T1 cell line, both with and without the chemotherapeutic agents. Our results showed no significant difference in anticancer activity between the illuminated and non-illuminated conditions at lower concentrations. However, as the concentration of the SWCNTs increased, we observed a corresponding rise in toxicity and a reduction in cell survival in the absence of radiation. Importantly, this effect was enhanced in the presence of radiation, resulting in a significant decline in cell viability compared to conditions without irradiation. Our findings indicate that incorporating SWCNT-Au nanoparticles improves the efficacy of radiotherapy. The results from the MTT assay support that X-ray radiation, when combined with radiosensitizing nanoparticles, leads to enhanced cellular damage. This heightened damage is likely due to the increased generation of ROS in the presence of gold nanoparticles. Conclusion In this study, we designed and synthesized a system that utilizes carbon nanotubes as a transporter for CUR and a substrate for Au nanoparticles, which function as radiation sensitizers for cancer treatment. The goal was to promote the efficacy of chemotherapy and radiation therapy concurrently protecting healthy tissues. We successfully prepared SWCNTs-Au and loaded CUR onto them. The synthesis of the nanoparticles was confirmed using various techniques. TEM determined the shape and size of the gold nanoparticles on SWCNTs-Au, while XRD patterns revealed the expected peaks for both SWCNTs and Au nanoparticles. FTIR and UV-Vis spectroscopy confirmed the characteristic absorption bands of each component. Release studies demonstrated pH-sensitive release, and in vitro tests, including hemolysis and the MTT assay on the HFF-2 cell line, indicated dose-dependent toxicity. The results show that X-ray radiation inflicts greater damage to cells in the presence of the radiation-sensitizing nanoparticles. This system produces secondary electron cascades and increases intracellular ROS, leading to enhanced cell death. Our hypothesis was that combining chemotherapy with nanoparticles that function as both drug carriers and radiosensitizers could offer promising treatment opportunities. The combination of chemotherapy and radiation therapy with nanoparticles demonstrated a greater effect compared to radiation therapy alone. In summary, our investigations validated the successful synthesis of nanoparticles, and the results indicated that increasing nanoparticle concentrations positively affects cell viability. Breast cancer cells experienced greater toxicity when exposed to both nanoparticles and X-ray exposure. Declarations Competing interests The authors declare that they have no competing interests. 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. Author Contribution Hossein Danafar: Designed the project, analyzed of data, and wrote the main manuscript textali mohammadi: analyzed of datanegin hashemi: Performed of in vitro cell culture studyzahra asghariha: analyzed of datamarzieh hosseini: Performed of synthesis of nanoparticles Acknowledgment This work was supported by Zanjan University of Medical Sciences. Data Availability Data availabilityThe datasets used during the current study available from the corresponding author on reasonable request. References Son, K.H., J.H. Hong, and J.W. Lee, Carbon nanotubes as cancer therapeutic carriers and mediators. International journal of nanomedicine, 2016: p. 5163-5185. Sun, Y.-S., et al., Risk factors and preventions of breast cancer. International journal of biological sciences, 2017. 13(11): p. 1387. Talib, W.H. and A.M. Mahasneh, Combination of Ononis hirta and Bifidobacterium longum decreases syngeneic mouse mammary tumor burden and enhances immune response. Journal of Cancer Research and Therapeutics, 2012. 8(3): p. 417-423. Talib, W.H., Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation. Nutrition, 2017. 43: p. 89-97. Talib, W.H. and A.M. Mahasneh, Antimicrobial, cytotoxicity and phytochemical screening of Jordanian plants used in traditional medicine. Molecules, 2010. 15(3): p. 1811-1824. Nounou, M.I., et al., Breast cancer: conventional diagnosis and treatment modalities and recent patents and technologies. Breast cancer: basic and clinical research, 2015. 9: p. BCBCR. S29420. Das, M., et al., Carbon nanotube embedded cyclodextrin polymer derived injectable nanocarrier: A multiple faceted platform for stimulation of multi-drug resistance reversal. Carbohydrate polymers, 2020. 247: p. 116751. Kitayama, Y., et al., In vivo stealthified molecularly imprinted polymer nanogels incorporated with gold nanoparticles for radiation therapy. Journal of Materials Chemistry B, 2022. 10(35): p. 6784-6791. Zarrintaj, P., et al., Poloxamer: A versatile tri-block copolymer for biomedical applications. Acta biomaterialia, 2020. 110: p. 37-67. Servatan, M., et al., Zeolites in drug delivery: Progress, challenges and opportunities. Drug Discovery Today, 2020. 25(4): p. 642-656. Mohammed, S.N., A.M. Mohammed, and K.F. Al-Rawi, Novel combination of multi-walled carbon nanotubes and gold nanocomposite for photothermal therapy in human breast cancer model. Steroids, 2022. 186: p. 109091. Zoi, V., et al., The role of curcumin in cancer treatment. Biomedicines, 2021. 9(9): p. 1086. Talib, W.H., et al., Role of curcumin in regulating p53 in breast cancer: An overview of the mechanism of action. Breast Cancer: Targets and Therapy, 2018: p. 207-217. Sun, C., et al., Preparation, characterization and stability of curcumin-loaded zein-shellac composite colloidal particles. Food chemistry, 2017. 228: p. 656-667. Anand, P., et al., Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer letters, 2008. 267(1): p. 133-164. Hussain, Y., et al., Curcumin–cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytotherapy Research, 2021. 35(12): p. 6514-6529. Yin, Z., et al., The relevant approaches for aligning carbon nanotubes. Micromachines, 2022. 13(11): p. 1863. Baghel, P., A.K. Sakhiya, and P. Kaushal, Ultrafast growth of carbon nanotubes using microwave irradiation: characterization and its potential applications. Heliyon, 2022. 8(10). Wang, J., et al., Multi-shelled metal oxides prepared via an anion-adsorption mechanism for lithium-ion batteries. Nature Energy, 2016. 1(5): p. 1-9. Beik, J., et al., Gold nanoparticles in combinatorial cancer therapy strategies. Coordination Chemistry Reviews, 2019. 387: p. 299-324. A. Mohammadi, et al., Synthesis of curcumin loaded single walled carbon nanotubes: characterization and anticancer effects in vitro, Results in Chemistry (2024) 101370. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-5354865","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":375894268,"identity":"c446dcdc-8937-454f-a388-928b076f55e0","order_by":0,"name":"Ali Mohammadi","email":"","orcid":"","institution":"Zanjan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Mohammadi","suffix":""},{"id":375894270,"identity":"0dcfbf43-4326-4a76-8e6f-b7531171a959","order_by":1,"name":"Negin Hashemi","email":"","orcid":"","institution":"Zanjan University of Medical 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Danafar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYDCCA0BcwcAgBxdgI0rLGQYGY9K1JDYQ7S6+42cPfjhQcy99/ozs5A8MNXYMfNIH8GuRPJOXLHHgWHFu44zcbRIMx5IZ2PgS8GsxOJBjIP2BLSG3WSJ3G9AjBxjYeAg4zOD8G+MfB/4lpLNJ5G7+wPCPGC03cswkDrYlJPBI5G6QYGwjQovkjTdmFgf7Egxn8LzdJpHYl8xDUAvf+RzjGwe+JcjLtwMd9uGbnZx8DwEtqCCBgYGQHaNgFIyCUTAKiAEAszVAxgydCC8AAAAASUVORK5CYII=","orcid":"","institution":"Zanjan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Hossein","middleName":"","lastName":"Danafar","suffix":""}],"badges":[],"createdAt":"2024-10-29 13:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5354865/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5354865/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68751413,"identity":"76388f6c-8530-4444-abfc-e34484848a2a","added_by":"auto","created_at":"2024-11-11 16:13:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":124047,"visible":true,"origin":"","legend":"\u003cp\u003eTEM image showing SWCNTs combined with Au nanoparticles.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/203c255d14e1ba748dbcd582.png"},{"id":68751492,"identity":"a7af3fa3-15fb-4555-9863-f910dbf2c62c","added_by":"auto","created_at":"2024-11-11 16:13:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17336,"visible":true,"origin":"","legend":"\u003cp\u003eShows the UV-Vis analysis of SWCNT-Au nanoparticles.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/c9ac2ef26e6f9262f5492a09.png"},{"id":68751542,"identity":"d9340306-6028-4665-a32b-3f93ad642e72","added_by":"auto","created_at":"2024-11-11 16:13:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51227,"visible":true,"origin":"","legend":"\u003cp\u003eShows the FTIR spectra for CUR, SWCNT-Au-CUR, and SWCNT-Au.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/26ceaa5c37b40ded60ffcc1b.png"},{"id":68751495,"identity":"816d11ac-7b4c-4463-b413-c170f0681f9f","added_by":"auto","created_at":"2024-11-11 16:13:22","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":22417,"visible":true,"origin":"","legend":"\u003cp\u003eXRD analysis of SWCNTs functionalized with Au nanoparticles\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/79585cce370641eedd265044.png"},{"id":68751487,"identity":"70cebd8c-56be-4df3-a038-7d02981ec99d","added_by":"auto","created_at":"2024-11-11 16:13:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":13432,"visible":true,"origin":"","legend":"\u003cp\u003eThe diagram shows how CUR is released in a simulated environment that resembles the conditions of the body and a cancerous tumor.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/ce50575dfa94e71e08b0f74a.png"},{"id":68751493,"identity":"5319bb25-bd28-4b58-83c1-1ad4952c10cc","added_by":"auto","created_at":"2024-11-11 16:13:22","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":11804,"visible":true,"origin":"","legend":"\u003cp\u003eThe hemolysis percentage of the SWCNTs was both designed and measured.\u003c/p\u003e","description":"","filename":"image7.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/1436d4247c964ae200f446f0.png"},{"id":68751496,"identity":"12e216ea-5dc5-41ee-a5df-6efd1a8a6849","added_by":"auto","created_at":"2024-11-11 16:13:22","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":12650,"visible":true,"origin":"","legend":"\u003cp\u003eCytotoxicity assessment of the engineered SWCNTs on HFF-2 cells. The symbol 'ns' indicates no significant differences in the observed results, while '****' denotes a significant difference with p-values.\u003c/p\u003e","description":"","filename":"image8.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/cc51c63d8f5d05d19da6dec9.png"},{"id":68751494,"identity":"5f618628-1aa3-46be-82ba-52926137c572","added_by":"auto","created_at":"2024-11-11 16:13:22","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":24449,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival of 4T1 cells with and without sensitizing nanoparticles and X-ray radiation. The significance levels are indicated as follows: ns, *, **, ***, and **** correspond to the following statistical significance levels: \"ns\" denotes no significant difference, while \"*\" shows a significant difference with a p-value of 0.05; \"**\" represents a significant difference with a p \u0026lt; 0.01; \"***\" signifies a significant difference with a p \u0026lt; 0.001; and \"****\" shows a major difference with a p \u0026lt; 0.0001.\u003c/p\u003e","description":"","filename":"image9.png","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/bc9c2687fdfa76db0b498813.png"},{"id":68944875,"identity":"1f41adac-9610-4ff4-8dc0-4c97cd01948e","added_by":"auto","created_at":"2024-11-13 19:31:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":725653,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5354865/v1/aca5b35c-060c-4af4-b8a5-adaccae9e441.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"SWCNTs functionalized with gold nanoradiosensitizers as radiosensitizers for enhanced radiotherapy in breast cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCancer has been recognized as a complex disease that poses a serious threat to human life [1]. Breast cancer is the most prevalent type of malignancy among women [2]. Various treatment options and medications have been utilized to combat this intense disease including surgery, radiotherapy and chemotherapy, each presenting its own set of challenges and limitations [3\u0026ndash;6]. Radiation therapy, as a conventional treatment method has the potential to cause unfavorable side effects on surrounding healthy tissues. Chemotherapy is a widely employed approach for managing cancer, Involving the administration of single or multiple drugs. Unfortunately, this method also has drawbacks such as multidrug resistance (MDR), poor pharmacokinetic profile of anticancer drugs and a detrimental impact on normal cells [7]. To ameliorate the effectiveness of these traditional therapeutic approaches, utilizing radiation sensitizers such as carbon nanotubes and gold nanoparticles is recommended. Enhancing the absorption of radiation by cancer cells while minimizing the impact on non-cancerous cells is one of the most important advantages of these therapeutic approaches [8]. In contrast, these nanotubes possess the potential to act as carriers for delivering anti-cancer drugs to cancerous cells in a manner that leads fewer negative side effects compared to treatment with chemotherapy as a monotherapy [9, 10]. This novel approach demonstrates promise in the management of these issues [11]. In this study, curcumin has been Investigated as a candidate for anticancer drugs that exhibit poor pharmacokinetic properties. Curcumin is an active ingredient of the turmeric plant that possesses various effects, such as: antioxidant, anti-inflammatory and anticancer effects [12\u0026ndash;14]. Curcumin impacts cancer cells through over 100 molecular pathways, including the downregulation of receptors such as HER-2, modulation of enzymes like COX-2 and ATPase, regulation of transcription factors like NF-kB and regulation of inflammatory cytokines such as IL-1 and IL-2 [15]. Furthermore, curcumin increases tumor sensitivity to medication and promotes cell death.[16]. Recent advancements in nanotechnology and these innovative techniques such as CNT-Au have shown potential for achieving greater efficacy with fewer side effects in cancer treatment. Sumio Iijima discovered multi-walled carbon nanotubes (MWCNTs) using electron microscopy in 1991. Subsequently, in 1993, Bethune discovered single-walled carbon nanotubes (SWCNTs) [17, 18]. Carbon nanotubes serve as carriers for delivering anticancer drugs, enhancing the specificity of treatment and improving the pharmacokinetic properties of these drugs, such as dissolution and stability [1, 19]. Gold nanoparticles, as radiation sensitizers, play a vital role in this treatment approach by reducing the dosage administered to non-cancerous cells. Moreover, these nanoparticles aid in the degradation of cancer cell DNA and enhance the treatment process through apoptosis induction [20]. Therefore, the objective of this study is to create gold nanoparticles and nanotubes for use as radiation sensitizers, intending to utilize them as a delivery system for curcumin in a combined chemotherapy and radiation therapy approach that leverages the strengths and mitigates the weaknesses of each treatment modality. This study will primarily assess response rates and evaluate the benefits and harms of this strategy.\u003c/p\u003e"},{"header":"Method and Materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMaterials\u003c/h2\u003e \u003cp\u003eMTT was acquired from Sigma Aldrich, a leading chemical supplier in the United States, Curcumin and dialysis bags were purchased from Merck KGaA, a global pharmaceutical and chemical company based in Darmstadt (Germany), The HFF-2 and the 4T1 were procured from the Pasteur Institute of Iran, a renowned research institution in the Middle East, Ethanol was procured from Kimia alcohol, a domestic supplier in Iran. Growth medium was acquired from Gibco, a leading life science technology company based in Germany.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMethods\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSWCNT synthesis\u003c/h2\u003e \u003cp\u003eFor the synthesis and purification of SWCNTs functionalized with Fe\u0026ndash;Mo catalyst, we adopted a methodology previously reported [21].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSynthesis of SWCNTs functionalized with gold nanoparticles\u003c/h3\u003e\n\u003cp\u003eGold nanoparticles were synthesized on a SWCNTs substrate by adding 0.9 mL of 1% sodium citrate solution and 1.036 mL of 0.45% HAuCL4 solution dropwise to a solution containing 4.7 mg of oxidized SWCNTs. A drop of 0.21 mg/mL NaBH4 solution was then added to the reaction mixture, which was stirred for 12 hours at 25\u0026deg;C. The formation of gold nanoparticles was indicated by a change in solution color to cherry. The solution was purified by dialysis for 48 hours.\u003c/p\u003e\n\u003ch3\u003eCurcumin-loaded SWCNTs -Au\u003c/h3\u003e\n\u003cp\u003eCurcumin(CUR) (4 mg) was dissolved in 1.25 mL of acetone and added dropwise to a suspension of 20 mg of SWCNTs-Au in water. The result compound was stirred at 25\u0026deg;C for 24 hours, then heated and centrifuged to remove any unbound CUR.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDiscovering the structure, physical and chemical properties\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eTransmission Electron Microscopy (TEM)\u003c/h2\u003e \u003cp\u003eThis technique enables the direct observation of nanoparticle morphology and size, as well as an understanding of their distribution and the degree of particle accumulation. Sample preparation involves first creating a dilute solution of nanoparticles in isopropyl alcohol or water. The resulting liquid was then dispersed and dried onto a carbon-coated grid. The analysis was then conducted using a TEM (Cambridge 360\u0026ndash;1990 Stereo Scan Instrument, EDS, CA).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eUV-Vis analysis\u003c/h3\u003e\n\u003cp\u003eUV-Vis was used to analyze the quantitative properties of synthesized SWCNTs -Au, CUR, and SWCNTs -Au-CUR. Measurements were taken using a GENESYS10S spectrophotometer (Thermo Fisher Scientific, Madison, Wisconsin) over a wavelength range of 200\u0026ndash;600 nm.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFTIR analysis\u003c/h2\u003e \u003cp\u003eFTIR spectroscopy was used to detect polar functional groups in the synthesized materials. A Tensor 27 FT-IR spectrometer (Bruker, Biotage, Germany) was used to measure the infrared absorption spectra over a wavenumber range of 4000\u0026thinsp;\u0026minus;\u0026thinsp;400\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{cm}^{-1}\\)\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eXRD analysis\u003c/h2\u003e \u003cp\u003eXRD analysis of SWCNTs was performed using a D8-advance diffractometer (Bruker AXS) with Cu-Kα radiation (λ\u0026thinsp;=\u0026thinsp;1.542 \u0026Aring;). The XRD data were collected over a 2θ range of 5 to 80 degrees.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDrug Loading\u003c/h2\u003e \u003cp\u003eTo load curcumin onto the primary nanocarrier system, 1 mg of SWCNTs -Au-CUR was dispersed in 2 mL of ethanol and incubated at 37\u0026deg;C for 24 hours. The mixture was then centrifuged at 5,000 rpm for 10 minutes to remove the supernatant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eCUR Release Study\u003c/h2\u003e \u003cp\u003eThe drug release profile was examined under two buffer conditions: physiological pH (7.4) and a tumor tissue simulator (pH 4.7). 1 mL of the synthetic SWCNTs -Au-CUR (containing 4 mg) was placed in a dialysis bag with a molecular weight cutoff of 12 kDa. The bag was then placed in 25 mL of a phosphate-ethanol buffer and placed in a shaking incubator at 100 rpm and 37\u0026deg;C. These procedures were conducted for both pH conditions with three repetitions. At predetermined time intervals, 1 mL of the solution was withdrawn from the outer chamber. The light absorption of the sample was measured at a wavelength of 430 nm using a UV-Vis spectrophotometer, and the sample was subsequently returned to the reaction container.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eBiocompatibility assessment\u003c/h2\u003e \u003cp\u003eThe biocompatibility of the synthesized SWCNTs -Au was assessed \u003cem\u003ein vitro\u003c/em\u003e using hemolysis and cytotoxicity tests on a healthy cell line.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ehemolysis\u003c/h2\u003e \u003cp\u003eThe hemolysis test assesses the compatibility of nanoparticles with blood. This test involves mixing red blood cells with various concentrations of the prepared SWCNTs -Au, followed by a 4-hour incubation period at 37\u0026deg;C with gentle shaking. The absorbance of the supernatant at 540 nm was measured after deionized water (positive control) and PBS solution (negative control) were used to incubate the samples. The samples were then centrifuged at 1300 rpm for 15 minutes. Each concentration was evaluated in triplicate, and the percentage of hemolysis for each sample was calculated.\u003c/p\u003e \u003cp\u003e\u003cimg 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\" height=\"39\" width=\"245\"\u003e\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of Cytotoxic Effects on non-cancerous Cells\u003c/h2\u003e \u003cp\u003eThe cytotoxicity effects of the synthesized SWCNTs -Au on the HFF-2 cell line was evaluated using the MTT assay. Healthy Cells were treated with various concentrations of the SWCNTs -Au, with each concentration being tested in five replicates.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eIn vitro therapeutic effects\u003c/h2\u003e \u003cp\u003e4T1 cells (7,000 cells/well) were plated in 96-well plates and then incubated with various concentrations of nanoparticles for 4 hours. After washing with PBS, selected groups were exposed to X-rays at a dose of 6 Gy. All cells were then incubated for an additional 12 hours, and cell viability was assessed using the MTT test.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis of CUR loaded SWCNTs-Au nanoparticles\u003c/h2\u003e \u003cp\u003eWe synthesized and functionalized SWCNTs with gold nanoparticles in this study. Subsequently, the developed SWCNTs -Au was loaded with CUR.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eMorphological assessment\u003c/h2\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003eTEM\u003c/h2\u003e \u003cp\u003eTEM imaging was used to characterize CWNTs-Au-CUR nanoparticles. This technique utilizes high-energy electrons to interact with the nanoparticles, allowing for the detailed examination of structures at the nanometer scale.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the TEM images of the SWCNTs-Au-CUR nanoparticles. The images clearly show the formation of spherical nanoparticles supported by the single-walled carbon nanotube substrate.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eUV-Vis\u003c/h2\u003e \u003cp\u003eThe UV-Vis spectrum showed characteristic peaks for curcumin at 430 nm, SWCNT-Au at 245 nm, and SWCNT-Au-CUR at 232\u0026ndash;245 nm. The presence of both CUR and SWCNT-Au peaks in the SWCNT-Au-CUR spectrum confirmed the successful loading of CUR into the SWCNTs -Au.\u003c/p\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eFTIR\u003c/h2\u003e \u003cp\u003eFigure 3 presents the FTIR analysis of the SWCNTs-Au-CUR nanoparticles FTIR analysis revealed characteristic peaks corresponding to O-H stretching vibrations (3450 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e), aromatic C\u0026thinsp;=\u0026thinsp;C stretching vibrations (1581\u0026thinsp;\u0026minus;\u0026thinsp;1423 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e), and Al2O3 vibrational modes (1640 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e), consistent with previous studies [21]. Furthermore, peaks at 521 and 649 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{cm}^{-1}\\)\u003c/span\u003e\u003c/span\u003e, indicative of gold nanoparticles encapsulated with CUR via carbon nanotube coating, were noted; however, these peaks were absent in the final product.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eXRD\u003c/h2\u003e \u003cp\u003eThe XRD pattern of the nanoparticles, presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e, aligns with the standard XRD profiles for Au and SWCNTs. This is consistent with our previous study on SWCNTs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eDrug-Loading\u003c/h2\u003e \u003cp\u003eThe drug loading efficiency was determined to be 14.27% curcumin.\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:drug\\:loading\\:content\\left(\\%\\right)=\\frac{weight\\:of\\:the\\:drug\\:in\\:nanoparticles}{weight\\:of\\:the\\:nanoparticles\\:with\\:drug}\\times\\:100$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eDrug release study\u003c/h2\u003e \u003cp\u003eThe release kinetics of curcumin have been studied in two PBS-ethanol buffer systems with pH values of 7.4 and 4.7. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e, curcumin release from the nanoparticles is relatively slow in both environments, with the highest release occurring in the acidic buffer. After 24 hours, about 39% of CUR was released in the neutral pH buffer, while the acidic environment resulted in approximately 56% release during the same period. These results indicate a pH-dependent release mechanism, where acidic conditions enhance CUR release. The differences in release can be attributed to two key factors: the solubility of CUR in the buffer and the environmental condition\u0026rsquo;s ability to disrupt interactions between CUR and the nanoparticle carrier. Thus, the extent of drug release is primarily influenced by the ability of the environmental parameters to weaken the binding interactions between the drug and the SWCNTs.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eHemolysis\u003c/h2\u003e \u003cp\u003eIn our biocompatibility study, we assessed the hematotoxicity of the synthesized SWCNTs (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Various concentrations of the SWCNTs were formulated with corresponding amounts of curcumin in each. The results showed that the SWCNTs had a dose-dependent response up to 200 \u0026micro;g/mL. Notably, the toxicity observed was less than 5%, indicating that the SWCNTs is safe for use.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003eCytotoxicity evaluation in HFF-2 cells\u003c/h2\u003e \u003cp\u003eWe investigated the toxicity of nanoparticles on non-cancerous embryonic fibroblast cells using the MTT assay (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e). Our results showed that the toxicity of SWCNT-Au nanoparticles increases with higher concentrations. Specifically, exposure of HFF-2 cells with varying nanoparticle concentrations revealed a direct relationship between SWCNT-Au concentration and cytotoxicity. The control group exhibited no important differences when subjected to curcumin at various concentrations of 4, 15, and 20 \u0026micro;g/mL. This lack of effect may be due to curcumin's low efficacy as an anticancer agent, its limited solubility, or its inadequate cellular penetration. However, the results suggest that CUR does not cause toxicity in HFF-2 cells at concentrations of 20 \u0026micro;g/mL or lower.\u003c/p\u003e \u003cp\u003e \u003cem\u003eTherapeutic Effects on\u003c/em\u003e 4T1 \u003cem\u003eCells: With and Without X-Ray Radiation\u003c/em\u003e\u003c/p\u003e \u003cp\u003eIn this study, we evaluated cell viability at nanoparticle concentrations of 25 \u0026micro;g/mL, 75 \u0026micro;g/mL, and 100 \u0026micro;g/mL, alongside X-ray irradiation at a dose of 6 Gy (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e). The anticancer effectiveness of the developed SWCNTs was assessed using the 4T1 cell line, both with and without the chemotherapeutic agents. Our results showed no significant difference in anticancer activity between the illuminated and non-illuminated conditions at lower concentrations. However, as the concentration of the SWCNTs increased, we observed a corresponding rise in toxicity and a reduction in cell survival in the absence of radiation. Importantly, this effect was enhanced in the presence of radiation, resulting in a significant decline in cell viability compared to conditions without irradiation. Our findings indicate that incorporating SWCNT-Au nanoparticles improves the efficacy of radiotherapy. The results from the MTT assay support that X-ray radiation, when combined with radiosensitizing nanoparticles, leads to enhanced cellular damage. This heightened damage is likely due to the increased generation of ROS in the presence of gold nanoparticles.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we designed and synthesized a system that utilizes carbon nanotubes as a transporter for CUR and a substrate for Au nanoparticles, which function as radiation sensitizers for cancer treatment. The goal was to promote the efficacy of chemotherapy and radiation therapy concurrently protecting healthy tissues. We successfully prepared SWCNTs-Au and loaded CUR onto them. The synthesis of the nanoparticles was confirmed using various techniques. TEM determined the shape and size of the gold nanoparticles on SWCNTs-Au, while XRD patterns revealed the expected peaks for both SWCNTs and Au nanoparticles. FTIR and UV-Vis spectroscopy confirmed the characteristic absorption bands of each component. Release studies demonstrated pH-sensitive release, and \u003cem\u003ein vitro\u003c/em\u003e tests, including hemolysis and the MTT assay on the HFF-2 cell line, indicated dose-dependent toxicity. The results show that X-ray radiation inflicts greater damage to cells in the presence of the radiation-sensitizing nanoparticles. This system produces secondary electron cascades and increases intracellular ROS, leading to enhanced cell death. Our hypothesis was that combining chemotherapy with nanoparticles that function as both drug carriers and radiosensitizers could offer promising treatment opportunities. The combination of chemotherapy and radiation therapy with nanoparticles demonstrated a greater effect compared to radiation therapy alone. In summary, our investigations validated the successful synthesis of nanoparticles, and the results indicated that increasing nanoparticle concentrations positively affects cell viability. Breast cancer cells experienced greater toxicity when exposed to both nanoparticles and X-ray exposure.\u003c/p\u003e "},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003ch2\u003eDeclaration of competing interest\u003c/h2\u003e \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\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHossein Danafar: Designed the project, analyzed of data, and wrote the main manuscript textali mohammadi: analyzed of datanegin hashemi: Performed of in vitro cell culture studyzahra asghariha: analyzed of datamarzieh hosseini: Performed of synthesis of nanoparticles\u003c/p\u003e\u003ch2\u003eAcknowledgment\u003c/h2\u003e \u003cp\u003eThis work was supported by Zanjan University of Medical Sciences.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData availabilityThe datasets used during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSon, K.H., J.H. Hong, and J.W. Lee, Carbon nanotubes as cancer therapeutic carriers and mediators. International journal of nanomedicine, 2016: p. 5163-5185.\u003c/li\u003e\n\u003cli\u003eSun, Y.-S., et al., Risk factors and preventions of breast cancer. International journal of biological sciences, 2017. 13(11): p. 1387.\u003c/li\u003e\n\u003cli\u003eTalib, W.H. and A.M. Mahasneh, Combination of Ononis hirta and Bifidobacterium longum decreases syngeneic mouse mammary tumor burden and enhances immune response. Journal of Cancer Research and Therapeutics, 2012. 8(3): p. 417-423.\u003c/li\u003e\n\u003cli\u003eTalib, W.H., Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation. Nutrition, 2017. 43: p. 89-97.\u003c/li\u003e\n\u003cli\u003eTalib, W.H. and A.M. Mahasneh, Antimicrobial, cytotoxicity and phytochemical screening of Jordanian plants used in traditional medicine. Molecules, 2010. 15(3): p. 1811-1824.\u003c/li\u003e\n\u003cli\u003eNounou, M.I., et al., Breast cancer: conventional diagnosis and treatment modalities and recent patents and technologies. Breast cancer: basic and clinical research, 2015. 9: p. BCBCR. S29420.\u003c/li\u003e\n\u003cli\u003eDas, M., et al., Carbon nanotube embedded cyclodextrin polymer derived injectable nanocarrier: A multiple faceted platform for stimulation of multi-drug resistance reversal. Carbohydrate polymers, 2020. 247: p. 116751.\u003c/li\u003e\n\u003cli\u003eKitayama, Y., et al., In vivo stealthified molecularly imprinted polymer nanogels incorporated with gold nanoparticles for radiation therapy. Journal of Materials Chemistry B, 2022. 10(35): p. 6784-6791.\u003c/li\u003e\n\u003cli\u003eZarrintaj, P., et al., Poloxamer: A versatile tri-block copolymer for biomedical applications. 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Mohammadi, et al., Synthesis of curcumin loaded single walled carbon nanotubes: characterization and anticancer effects in vitro, Results in Chemistry\u003cbr\u003e (2024) 101370.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Chemotherapy, Radiation sensitizers, Single-wall carbon nanotubes, Curcumin","lastPublishedDoi":"10.21203/rs.3.rs-5354865/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5354865/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBreast cancer is the most common and significant threat affecting women globally. Traditional methods have been widely used in cancer treatment for many years. However, the unavoidable side effects of these approaches are undeniable. Nanotechnology and carbon nanotubes offer the potential to improve traditional cancer treatments by reducing side effects and enhancing efficacy. In this project, we investigated the potential of Single-Walled Carbon Nanotubes (SWCNTs) as advanced delivery systems for chemotherapy agents directly within tumors, as well as their role as substrates for developing radiation sensitizers to enhance the efficacy of radiation therapy alone. To confirm the successful formation of the nanoparticles, we conducted various techniques such as Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), UV-Visible spectroscopy and X-Ray Diffraction (XRD) to ensure accurate verification. To evaluate the cytotoxicity of SWCNTs -Au-CUR nanoparticles, we performed MTT and hemolysis assays. Subsequently, we assessed the effectiveness of the synthesized nanoparticles at different concentrations, with and without the aid of X-ray, against cancer cells. Observed results showed the correct creation and high efficacy of these nanoparticles on cancerous cells. It also showed that the presence of X-rays amplified nanoparticle toxicity, increased the ROS levels in the cancerous cells, and resulted in more effective induction of DNA damage.\u003c/p\u003e","manuscriptTitle":"SWCNTs functionalized with gold nanoradiosensitizers as radiosensitizers for enhanced radiotherapy in breast cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-11 16:11:35","doi":"10.21203/rs.3.rs-5354865/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"95845a74-d72f-40f4-88fa-45d691fb2550","owner":[],"postedDate":"November 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":40022948,"name":"Biological sciences/Cancer"},{"id":40022949,"name":"Biological sciences/Cell biology"},{"id":40022950,"name":"Physical sciences/Chemistry"},{"id":40022951,"name":"Physical sciences/Materials science"}],"tags":[],"updatedAt":"2024-11-13T19:23:39+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-11 16:11:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5354865","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5354865","identity":"rs-5354865","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}