Self-assembled multifunctional polymeric micelles for tumor-specific bioimaging and synergistic chemo-phototherapy of cancer

Abstract Integration of multiple therapies into one nanoplatform holds great promise to overcome the shortcomings of traditional single-modal therapy and achieve favorable antitumor efficacy. Herein, we constructed a dual receptor-targeting nanomicelle system with GSH-responsive drug release for precise fluorescence imaging and superior chemo-phototherapy of cancer. The synthetic amphiphilic hyaluronic acid derivative (FHSV) could self-assemble into nanomicelles in aqueous media. Then, paclitaxel (PTX) and photosensitizer IR780 iodide (IR780) were co-loaded into the micelles by a simple dialysis method. The resulting IR780/PTX/FHSV micelles with a particle size of 150.2 ± 6.9 nm exhibited excellent stability, GSH-responsive drug release and good photothermal/photodynamic efficacy. Once accumulated at the tumor sites, IR780/PTX/FHSV micelles efficiently entered tumor cells through receptor-mediated endocytosis and then rapidly release PTX and IR780 under GSH-rich tumor microenvironment. Upon NIR laser irradiation, IR780 produced local hyperthermia and sufficient reactive oxygen species to promote tumor cells apoptosis and necrosis. The results of in vitro and in vivo experiments consistently demonstrated that compared with single chemotherapy and phototherapy, the chemo-phototherapy could more efficiently kill tumor cells by synergistic antitumor effect. Therefore, our study provides a novel and efficient approach for multimodal treatment of malignant tumor.