Nanoscale Multivariate Metal–Organic Frameworks Amplify Oxidative Stress for Efficient Photodynamic Therapy of Cancer

Hypoxia, overexpression of endogenous hydrogen peroxide (H2O2), and dysregulation of glutathione (GSH) severely impair the efficacy of photodynamic therapy (PDT) in various cancer treatments. Herein, we construct a nanoscale multivariate metal–organic framework (MTV-MOF) by coordination chelation between Mn/Fe clusters and meso-tetra(4-carboxyphenyl)porphine (TCPP-H2), which can efficiently catalyze the intracellular over-expressed H2O2 and dysregulated GSH into oxygen (O2) and oxidized glutathione GSSG, respectively. The generated O2 is further converted to cytotoxic singlet oxygen (1O2) to kill tumor cells when irradiated under 660 nm near-infrared light, and the synergistic effect of GSH depletion further amplifies intracellular oxidative stress for cancer photodynamic therapy.