Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamical therapy or chemotherapy. In this study, we have developed a novel strategy to overcome tumor hypoxia induced radiotherapy tolerance. Specifically, a novel two-dimensional Pd@Au bimetallic core-shell nanostructures (TPAN) was employed for the sustainable and robust production of O2 in long-term via the catalysis of endogenous H2O2. Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR-II laser irradiation, to enhance the O2 production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: (i) NIR-II laser triggered SPR enhanced the catalysis of TPAN to produce O2 for relieving tumor hypoxia; (ii) high-Z element effect arising from Au and Pd to capture X-ray energy within tumor; (iii) TPAN affording X-ray, photoacoustic and NIR-II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation.

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