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Local hypoxia in solid tumors often results in resistance to radiotherapy (RT), in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide (Au@MnO2) core–shell nanoparticles with a polyethylene glycol (PEG) coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO2 nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO2 shell may trigger the decomposition of endogenous H2O2 in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO2-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO2-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.
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