The Radiosensitization Effect Of CuS/Au Nanoparticles Combined With Photothermal Therapy On Breast Cancer

Objective: To investigate the photothermal and radiosensitizing effects of（CuS/Au）nanoparticles（NPs）.Methods: Au,CuS,and（CuS/Au）NPs were synthesized for characterization using upto-date technologies and were analyzed for biosafety,respectively.The（CuS/Au）NP was studied for its in vitro photothermal effect,the lethal effect on and uptake by the murine mammary carcinoma cell line 4T1,and the transcytotic transport mechanism responsible for drug delivery into 4T1 cells.In addition,the radiosensitizing effect was evaluated by applying（CuS/Au）NPs to a 4T1 tumor model in DNA damage,colony formation,and cell viability and cytotoxicity assays based on radiotherapy（RT）and photothermal therapy（PTT）.Deep tumor penetration and temperature stimulation by near-infrared II（NIR-II）irradiation were detected in the presence of such（CuS/Au）NPs.The anaerobic environment of tumor tissue following NIR-II irradiation and the post-RT level of reactive oxygen species（ROS）in tumor tissue were evaluated to further investigate the mechanism of radiosensitization after（CuS/Au）NP-mediated PTT.A mouse 4T1 breast tumor model was constructed to analyze the efficacy of radio-photothermal therapy using（CuS/Au）NPs.Results: 1)（CuS/Au）NPs were successfully assembled.In tumor tissue,CuS NPs that were released from the p H-responsive（CuS/Au）NPs demonstrated desirable photothermal activity and directly induced in vitro tumor cell death through a temperature increase within the tumor.2)The（CuS/Au）NP-mediated photothermal temperature rise resulted in dilated blood vessels in the tumor,elevated oxygen levels in the hypoxic regions,and aggravated DNA damage and enhanced radiosensitivity induced by further enrichment of Au NPs in the tumor.In short,（CuS/Au）NPs in NIR-II PTT and RT as combination therapy produced satisfactory treatment outcomes with maximized radiosensitizing effect in the mouse 4T1 breast tumor model.Conclusions: Tumor microenvironment（TME）-responsive（CuS/Au）NPs directly kill tumor cells by mediating NIR-II PTT to generate high temperature which improves the hypoxic TME through tumor vasodilation and increased oxygen supply.During PTT,（CuS/Au）NPs further promote the enrichment of Au NPs in the tumor and improve RT efficacy.In radio-photothermal therapy,（CuS/Au）NPs demonstrate a greater radiosensitizing effect and good biosafety,which shows an exciting clinical prospect.