Au^I-incorporated metal-organic frameworks nanozymes for thioreduction and glutathione depletion-mediated efficient photoimmunotherapy

Tumor therapy has historically been a global research focus, with phototherapy garnered significant attention as a innovative treatment modality. However, the antioxidant defense system in the tumor microenvironment, characterized by excessive glutathione (GSH) and thiol-containing proteins, often limits the effectiveness of photodynamic therapy. In this study, we report the development of a new multifunctional integrated nanozyme with thioredoxin reductase-oxidase (TrxRox) and GSH-oxidase (GSHox)-like activities. This nanozyme, termed Au^I-incorporated MOFs, was synthesized by embedding monovalent Au nanozymes into a light-sensitive metal-organic framework (MOFs) structure using an in-situ oxidation-reduction method. The intergrated Au^I nanozyme exhibited inhibitory effects on TrxR and presented significant anti-tumor properties. Moreover, the integrated nanozyme also demonstrates peroxidase-like activity, catalyzing the decomposition of hydrogen peroxide (H₂O₂) into hydroxyl radicals (•OH). Additionally, this nanomedicine effectively depletes existing GSH and TrxR, thereby enhancing the efficacy of photodynamic and photothermal therapy. Notably, under light conditions, this nanozyme induces oxidative stress within cells, leading to apoptosis and necrosis of tumor cells. Of note, it triggers immunogenic cell death and activating antigen-presenting cells to convert cold tumors into hot tumors. Therefore, Au^I-incorporated MOFs nanozyme demonstrates promising potential in photoimmunotherapy, offering new insights and strategies for tumor therapy.