Oxygen‐Generating MnO2 Nanodots‐Anchored Versatile Nanoplatform for Combined Chemo‐Photodynamic Therapy in Hypoxic Cancer

Abstract Local hypoxia in tumors results in undesirable impediments for the efficiencies of oxygen‐dependent chemical and photodynamic therapy (PDT). Herein, a versatile oxygen‐generating and pH‐responsive nanoplatform is developed by loading MnO 2 nanodots onto the nanosystem that encapsulates g‐C 3 N 4 and doxorubicin hydrochloride to overcome the hypoxia‐caused resistance in cancer therapy. The loaded MnO 2 nanodots can react with endogenous acidic H 2 O 2 to elevate the dissolved oxygen concentration, leading to considerably enhanced cancer therapy efficacy. As such, the as‐prepared nanoplatform with excellent dispersibility and satisfactory biocompatibility can sustainably increase the oxygen concentration and rapidly release the encapsulated drugs in acid H 2 O 2 environment. In vitro cytotoxicity experiments show a higher therapy effect by the designed nanoplatform, when compared to therapy without MnO 2 nanodots under hypoxia condition, or chemical and photodynamic therapy alone with the presence of MnO 2 nanodots. In vivo experiments also demonstrate that 4T1 tumors can be very efficiently eliminated by the designed nanoplatform under light irradiation. These results highlight that the MnO 2 nanodots‐based nanoplatform is promising for elevating the oxygen level in tumor microenvironments to overcome hypoxia limitations for high‐performance cancer therapy.