Abstract：The application of photothermal agent copper sulfide nanoparticles (CuS) requires an increase in the drug concentration to achieve desired therapeutic effect. However, the increase of drug concentration would lead to more side effects, which limited clinical applications. In this study, erythrocytes were used as the carriers for CuS, which can rapidly respond to the laser, and tumor targeted release of CuS can increase photothermal effects. In this work, 40 mice bearing tumor were randomly divided into 4 groups, control group, laser treated group, CuS+laser group, CuS@ER+laser group, there were 10 mice in each group. According to the modified expansion method, the nano CuS was packed into erythrocytes, and the laser-responsive release behavior was investigated after lasered. The target behavior was examined with a in vivo imaging detection system for small animals and the photothermal therapy effect was detected by thermal imager. Additional outcome measures included tumor response rate, overall survival, and safety. It was found out that CuS was loaded into erythrocytes and the loading efficiency was 17.24%±0.98%. The biocompatibility of the CuS was improved due to the encapsulation of erythrocytes and the photothermal conversion efficiency was over 53% after 0.44 W/cm2 980 nm laser radiation. The concentration of CuS in the tumor after CuS@ER treatment was(0.061±0.007)μg/g, it was significantly higher than that of the free nano-CuS treatment (P<0.01), because of laser-response release behavior. The inhibitory rate of tumor growth for the CuS@ER group was 0.91 ± 0.02 with less side effects, as the temperature of the photothermal therapy increased. The survival rate of CuS@ER treatment was 90% after 48 days with less side effects. Our study provided a promising strategy to increased photothermal therapy without concede biocompatibility, by using an erythrocyte-inspired and laser-activatable platform.
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