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

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.e., 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) via suppressed expression of hypoxiainducible factor-1 alpha, 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-IIactivated chemotherapy. This work presents an efficient H2O2-driven oxygenerator for enhanced hypoxia-dampened chemotherapy and NIR-II photothermal therapy.

Automated summary

In this study, a bimetallic oxygen nanogenerator was developed to reduce multidrug resistance and efficiently eradicate tumors through oxygenation and synergistic chemo-photothermal therapy. The nanogenerator catalyzed oxygen generation from endogenous hydrogen peroxide, reducing drug exocytosis and resistance gene expression. Additionally, it enabled NIR-II photothermal therapy and NIR-II activated chemotherapy, demonstrating its potential in enhancing hypoxia-dampened chemotherapy.