NIR-II Driven Plasmon-Enhanced Catalysis for a Timely Supply of Oxygen to Overcome Hypoxia-Induced Radiotherapy Tolerance

Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamic therapy, or chemotherapy. In this study, a strategy is developed to overcome tumor hypoxia-induced radiotherapy tolerance. Specifically, a novel two-dimensional Pd@Au bimetallic core-shell nanostructure (TPAN) was employed for the sustainable and robust production of O-2 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 O-2 production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: 1) NIR-II laser triggered SPR enhanced the catalysis of TPAN to produce O-2 for relieving tumor hypoxia; 2) high-Z element effect arising from Au and Pd to capture X-ray energy within the tumor; and 3) 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.