Platinum Drug-Assisted Responsive Nanoscale Metal Phenolic Networks with Self-Sufficient ROS Amplification for Synergistic Tumor Therapy

Abstract Monotherapy is severely limited by tumor adaptive evolution and intrinsic heterogeneity, making synergistic therapeutic strategies urgently necessary. Herein, we developed a platinum-drug-assisted, tumor microenvironment-responsive nanoscale metal-phenolic network (OXPT@FeMPN) with self-sufficient reactive oxygen species amplification for precision multimodal synergistic therapy. OXPT@FeMPN stably loads oxaliplatin via combined physical and chemical interactions, with a drug loading efficiency of 19.8%, and enables tumor microenvironment-responsive drug release. The released oxaliplatin promotes hydrogen peroxide production, which is subsequently catalyzed by the OXPT@FeMPN nanozyme into hydroxyl radicals, enabling self-sufficient reactive oxygen species amplification in tumors. OXPT@FeMPN also depletes intratumoral glutathione, thereby suppressing tumor antioxidant defense. These cascade catalytic reactions ultimately trigger chemodynamic therapy (CDT). Moreover, OXPT@FeMPN exhibits a high photothermal conversion efficiency (η = 37.5%) under near-infrared irradiation, generating localized hyperthermia for photothermal therapy (PTT) and further enhancing CDT efficiency. In vitro, OXPT@FeMPN plus near-infrared irradiation markedly depleted intracellular glutathione and generated abundant reactive oxygen species, ultimately inducing tumor cells apoptosis. In vivo, this therapeutic strategy achieved 87.8% tumor inhibition with favorable biocompatibility. Collectively, this study presents a multimodal nanoplatform integrating chemotherapy, CDT, and PTT, overcoming the limitations of monotherapy and showing promise for the management of advanced tumors.