H2O2 Self-Supplementing and GSH-Depleting Nanoreactors Based on MoO3-x@Fe3O4-GOD-PVP for Photothermally Reinforced Nanocatalytic Cancer Therapy at the Second Near-Infrared Biowindow

Nanocatalytic therapy is an emerging strategy for combating various malignant tumors, which is limited by acid/H2O2 deficiency and overexpressed glutathione (GSH). Herein, the versatile MoO3-x@Fe3O4-GOD-PVP (MFGP) nanoreactors were developed to overcome the limitations of nanocatalytic therapy. First, MoO3-x nanoflakes were loaded with Fe(3)O(4 )nanozymes via electrostatic self-assembly and then decorated with glucose oxidase (GOD) and polyvinylpyrrolidone (PVP). At the tumor micro-environment (TME), nanocatalytic therapy can be performed by the nanoreactors triggering a sequence of catalytic reactions. The hydroxyl radicals (OH) generated by Fe3O4 nanozymes triggering the Fenton reaction can kill cancer cells. GOD could not only consume the glucose of the TME to starve the tumor but also in situ generate gluconic acid/H2O2 resulting in sustainable center dot OH production. In addition, overexpressed GSH, an antioxidant of cancer cells, would be effectively consumed via Mo triggering redox reactions. Importantly, due to the strong second near-infrared (NIR-II) absorption of MoO3-x nanoflakes, MFGP possessed an excellent photothermal property (photothermal conversion efficiency of 49.9%). The generated hyperthermia by MFGP can simultaneously enhance the Fenton reaction efficiency, GOD catalytic reaction, and GSH depletion. Extensive biomedical evaluations demonstrated the desirable tumor suppression effect based on hyperthermia-augmented nanocatalytic therapy. Overall, this work paves the way to the exploration of tumor nanocatalytic therapy.