The presence of hypoxia in tumors is characteristic of most solid tumors and it promotes not only tumor angiogenesis but also tumor cell invasion and metastasis. It also results in resistance of tumor tissue to radiation, leading to poor outcomes of tumor radiotherapy. Therefore, to address this conundrum, highly selective gold nanoclusters were prepared as fluorescent imaging agents and radiosensitizers and then loaded with tumor hypoxia-activated prodrugs to prepare nanoprobes which synergistically improved the anti-tumor efficacy by combining radiotherapy and hypoxia-activated therapy. The designed nanoprobes have ultra-small size, high selectivity for integrin αvβ3 receptor-positive tumor cells and tumor neovascular endothelial cells, and excellent fluorescence imaging performance. The experimental procedures were carried out in vitro and in vivo to demonstrate that the developed nanoprobes have a high level of biocompatibility, efficient radiosensitization effect, and anti-tumor efficacy at cell and tissue levels. The combined application of radiotherapy and hypoxia-activated therapy can overcome the radiation resistance caused by tumor hypoxia, compensate for the limitations of single radiotherapy, inhibit tumor growth, improve the efficacy of tumor radiotherapy, and provide new possibilities for the development of more precise and effective treatment strategies.
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