Cascade Tumor Therapy Platform for Sensitized Chemotherapy and Penetration Enhanced Photothermal Therapy

Abstract

As a stand-alone therapy strategy may not be sufficient for effective cancer treatment and a combination of chemotherapy with other therapies is a main trend in cancer treatment. A combination of chemotherapy and photothermal therapy (PTT) is reported here to achieve the goal of cascade multistage cancer treatment. A thermally responsive amphiphilic copolymer is designed and then a CuS nanoparticles (NPs)-based carbon monoxide (CO) photoinduced release system and doxorubicin (Dox) are encapsulated to construct the nanomedicine. The large-sized nanomedicine can accumulate in tumors after long circulation in vivo and will generate heat to act as a photothermal therapeutic agent by near infrared (NIR) light. Moreover, synergically release of CO and Dox is achieved and acted as a sensitized chemotherapeutic agent. The combination of PTT and chemotherapy sensitization can effectively eliminate active tumor cells in the periphery of the tumor. CuS NPs are also released after the degradation of nanomedicine and small-sized CuS NPs possess better tumor penetration and achieve penetration-enhanced PTT by further NIR irradiation, thereby effectively eliminating tumor cells inside solid tumors. Hence, cascade multistage cancer treatment of "combined PTT and chemotherapy sensitization"-"penetration-enhanced PTT" is achieved, and tumor cells are comprehensively and effectively eliminated.

Keywords: cascade therapy; penetration enhanced; photothermal therapy; sensitized chemotherapy; tumor therapy.