A Porous Bimetallic Au@Pt Core-Shell Oxygen Generator to Enhance Hypoxia-Dampened Tumor Chemotherapy Synergized with NIR-II Photothermal Therapy.

Abstract

The characteristic hypoxia of solid tumors and inadequate oxygen supply become a key causation of the resistance to chemotherapy in cancer treatment. Herein, a bimetallic oxygen nanogenerator, <i>i</i>.<i>e</i>., porous Au@Pt core-shell nanostructures, is particularly developed to reduce the multidrug resistance by oxygenating the tumor along with synergistic chemo-photothermal therapy for efficient tumor eradication. The porous platinum (Pt) shell was able to catalyze oxygen generation from endogenous hydrogen peroxide in the tumor, reducing the exocytosis of doxorubicin (DOX) <i>via</i> suppressed expression of hypoxia-inducible factor-1α, multidrug resistance gene 1, and P-glycoprotein. The strong absorbance of Au@Pt nanostructures in NIR window II enabled NIR-II photothermal therapy. Further incorporation of DOX into the mesopores of Au@Pt nanostructures with the assistance of phase change materials (PCM) led to the formulation of Au@Pt-DOX-PCM-PEG nanotherapeutics for NIR-II-activated chemotherapy. This work presents an efficient H₂O₂-driven oxygenerator for enhanced hypoxia-dampened chemotherapy and NIR-II photothermal therapy.