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Liposome coated hollow copper sulfide nano-enzyme enhances treatment of melanoma by photothermal therapy
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Abstract:
Objective: To construct hollow copper sulfide nanocarrier with lipid to improve the endocytosis efficiency of copper sulfide, and to further investigate the effect and mechanism of killing melanoma cells by chemodynamic therapy (CDT) combined with photothermal therapy (PTT) in near-infrared second region (NIR-II). Methods: Firstly, cationic liposome (LIP) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome coated copper sulfide nanocarriers (CuS@LIP). Secondly, the photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1064 nm laser irradiation. The catalytic activity of CuS@LIP to catalyze H2O2 was verified by detecting system of hydrogen peroxide (H2O2) and 3,3",5,5" -tetramethylbenzidine (TMB). Finally, the cell viability of B16-F10 melanoma cells were determined with a series of CuS and CuS@LIP with various concentration gradient under 1064 nm laser via CCK-8 method, and the appropriate CuS@LIP concentration was screened for subsequent experiments, and cell viability was detected by Calcein-AM/PI method and Annexin V-FITC/PI staining and flow cytometry were used to determine the apoptosis rate. Results: The average particle size of CuS@LIP was 178.23 ± 6.46 nm and the average Zeta potential was 20.47±0.93 mV. The highest temperature of 80 μg/mL CuS@LIP at 1064 nm laser irradiation was 65.4 ℃, which was higher than that of CuS at 63.4 ℃. The end point temperature of CuS@LIP is basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP has the same catalytic activity as CuS. The results of CCK-8 showed that CuS@LIP had no significant effect on the cell activity in vitro when it was less than 20 μg/ml, but the killing effect was significantly increased by 58.18% after laser irradiation(P<0.001). The rate of dead cells increased from 2.68% to 19.81% (P<0.001). The apoptosis rate was 19.34% in the NIR group compared with 13.36% in the non-light group (P<0.01). Conclusion: CuS@LIP can be endocytosed by melanoma cells with high efficiency, and maintain the catalytic property of H2O2 used in chemodynamic therapy. At the same time, the near infrared laser irradiation showed better anti-melanoma and killing effect of photothermal therapy. Therefore, CuS@LIP represents an excellent antitumor approach towards melanoma.
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