Site-Selective Photosynthesis of Ag–AgCl@Au Nanomushrooms for NIR-II Light-Driven O2- and O2•–-Evolving Synergistic Photothermal Therapy against Deep Hypoxic Tumors

Light-driven endogenous water oxidation has been considered as an attractive and desirable way to obtain O2 and reactive oxygen species (ROS) in the hypoxic tumor microenvironment. However, the use of a second near-infrared (NIR-II) light to achieve endogenous H2O oxidation to alleviate tumor hypoxia and realize deep hypoxic tumor phototherapy is still a challenge. Herein, novel plasmonic Ag–AgCl@Au core–shell nanomushrooms (NMs) were synthesized by the selective photodeposition of plasmonic Au at the bulge sites of the Ag–AgCl nanocubes (NCs) under visible light irradiation. Upon NIR-II light irradiation, the resulting Ag–AgCl@Au NMs could oxidize endogenous H2O to produce O2 to alleviate tumor hypoxia. Almost synchronously, O2 could react with electrons on the conduction band of the AgCl core to generate superoxide radicals (O2•–)for photodynamic therapy. Moreover, Ag–AgCl@Au NMs with an excellent photothermal performance could further promote the phototherapy effect. In vitro and in vivo experimental results show that the resulting Ag–AgCl@Au NMs could significantly improve tumor hypoxia and enhance phototherapy against a hypoxic tumor. The present study provides a new strategy to design H2O-activatable, O2- and ROS-evolving NIR II light-response nanoagents for the highly efficient and synergistic treatment of deep O2-deprived tumor tissue.