Oxygen Self-sufficient NIR-responsive Nanosystem for Enhanced PDT and Chemotherapy against Hypoxic Tumor

The efficacy of photodynamic therapy and chemotherapy is largely limited by oxygen deficient in the hypoxic tumor microenvironment. To solve these problems, we fabricated a novel NIR-responsive nanosystem which could co-delivery oxygen and anticancer drug DOX. Oxygen self-sufficient amphiphile (F-IR780-PEG) was first synthesized and subsequently utilized to load anticancer drug DOX to form nanoparticles (F/DOX nanoparticles). Due to the high oxygen capacity of such nanoparticles, the hypoxic tumor microenvironment was greatly modulated after these nanoparticles reached tumor region, and the results exhibited that hypoxia-inducible factor α (HIF-1α) was down-regulated and the expressions of P-glycoprotein (P-gp) was then reduced, which were in favor of chemotherapy. Under the light irradiation of 808 nm, IR780 could efficiently produce singlet oxygen to damage cancer cells by photodynamic therapy (PDT). Simultaneously, the IR780 linkage could be cleaved by singlet oxygen generated by itself and resulted in DOX release, which further caused cell damage by chemotherapy. With the combination of PDT and chemotherapy, F/DOX nanoparticles showed remarkable therapeutic efficacy in vitro and in vivo. Furthermore, the F/DOX nanoparticles are favorable for imaging-guided tumor therapy due to the inherent fluorescent property of IR780. We thus believe that the synergistic treatment described here leading to an ideal therapeutic approach to hypoxic tumor.