Hollow Mesoporous MnO₂ Nanospheres as Light Source-Free Carriers for Synergistic Starvation and Chemiexcited Photodynamic Tumor Therapy

Photodynamic therapy (PDT) has limitations for deep tumors that cannot be reached by an external excitation light source, and it is a feasible strategy to use chemical energy instead of an external laser to excite the photosensitizer. Herein, biodegradable self-supplying cascade reactors with hollow mesoporous manganese dioxide (HMnO 2 ) nanospheres as carriers were developed, which could improve the hypoxia characteristics of the tumor microenvironment (TME) for synergistic starvation therapy and chemiexcited PDT. The chemiluminescent substrate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO) made the generation of reactive oxygen species (ROS) no longer rely on external light sources. Glucose oxidase (GOx) catalyzed glucose to produce a large amount of hydrogen peroxide (H 2 O 2 ), which not only promoted the decomposition of the manganese dioxide shell to release the drugs but also produced oxygen (O 2 ) to improve the tumor microenvironment and also stimulated the activation of CPPO for promoting the photosensitizer chlorin e6 (Ce6) to convert O 2 into singlet oxygen ( 1 O 2 ), leading to the death of cancer cells. This cascade nanoreactor had a hydrodynamic diameter of approximately 140 nm, which greatly simplified the synthesis steps of nanoparticles and utilized the cascade reaction to maximize the efficacy of cancer treatment. Therefore, the self-supplying cascade strategy will provide a feasible and efficient way for cancer therapy in the future.