A Porous Au@Rh Bimetallic Core–Shell Nanostructure as an H₂O₂-Driven Oxygenerator to Alleviate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

In treatment of hypoxic tumors, oxygen-dependent photodynamic therapy (PDT) is considerably limited. Herein, a new bimetallic and biphasic Rh-based core–shell nanosystem (Au@Rh-ICG-CM) is developed to address tumor hypoxia while achieving high PDT efficacy. Such porous Au@Rh core–shell nanostructures are expected to exhibit catalase-like activity to efficiently catalyze oxygen generation from endogenous hydrogen peroxide in tumors. Coating Au@Rh nanostructures with tumor cell membrane (CM) enables tumor targeting via homologous binding. As a result of the large pores of Rh shells and the trapping ability of CM, the photosensitizer indocyanine green (ICG) is successfully loaded and retained in the cavity of Au@Rh-CM. Au@Rh-ICG-CM shows good biocompatibility, high tumor accumulation, and superior fluorescence and photoacoustic imaging properties. Both in vitro and in vivo results demonstrate that Au@Rh-ICG-CM is able to effectively convert endogenous hydrogen peroxide into oxygen and then elevate the production of tumor-toxic singlet oxygen to significantly enhance PDT. As noted, the mild photothermal effect of Au@Rh-ICG-CM also improves PDT efficacy. By integrating the superiorities of hypoxia regulation function, tumor accumulation capacity, bimodal imaging, and moderate photothermal effect into a single nanosystem, Au@Rh-ICG-CM can readily serve as a promising nanoplatform for enhanced cancer PDT.