Synergistic chemo-photodynamic therapy mediated by light-activated ROS-degradable nanocarriers

The combination of chemotherapy and photodynamic therapy (PDT) using polymeric nanocarriers is effective for improving therapeutic efficiency against cancer. Yet, in most reported cases, due to the lack of synergistic mechanisms, chemotherapy and PDT work independently rather than synergistically-the functions of chemotherapeutic drugs and photosensitizers in nanocarriers are independent when they are delivered to cancer cells. Here, we demonstrate the construction of reactive oxygen species (ROS)-degradable nanoparticles (NPs) based on phenylboronic pinacol ester-conjugated dextran (PPE-Dex) through a membrane-extrusion emulsification approach for the co-delivery of anticancer drug (e.g., doxorubicin, Dox) and photosensitizer (e.g., chlorin e6, Ce6). When exposed to 655 nm laser irradiation, ROS generated by encapsulated Ce6 not only induced a significant PDT effect in cancer cells, but also triggered the rapid oxidization and degradation of PPE-Dex, resulting in the quick release and enhanced intra-nuclei accumulation of Dox. In vitro cytotoxicity and combination index (CI) assay indicated that the PPE-Dex NPs offered remarkable synergistic therapeutic effects of Dox and Ce6 against cancer cells under irradiation. Furthermore, the drug release profiles can be well regulated by changing the irradiation time to satisfy different demands in various treatment programs. Our results demonstrated that such ROS-degradable polymeric NPs with light-activated disassembly capability are promising carriers for synergistic photodynamic-chemo therapy in cancer therapy.