Engineering Structural Metal–Organic Framework for Hypoxia-Tolerant Type I Photodynamic Therapy against Hypoxic Cancer

Photodynamic therapy (PDT) performance is always impaired by the characteristic hypoxic tumor microenvironment (TME) of solid tumors. To surmount this intractable issue, herein, we report the design of an hypoxia-tolerant MOF@TiO2 (MOF, metal–organic framework) photosensitizer (PS) consisting of TiO2 nanoparticles-decorated zirconium(IV)-based meso-tetra(4-carboxyphenyl) porphine (TCPP) MOF, also demonstrate its detailed radicals generation mechanism under hypoxic conditions and validate its superb anticancer efficiency for in vivo hypoxic solid cancer ablation. Under laser irradiation, the MOF@TiO2 PS generates singlet oxygen (1O2) through an oxygen-dependent type II mechanism by energy transfer. Notably, it is also able to produce superoxide radicals (O2• –) and hydroxyl radicals (•OH) via oxygen-independent type I mechanism by electron transfer under severely hypoxic conditions because of the staggering energy band edges between TCPP and TiO2. Thus, the advanced nanosystems can self-regulate to maximize PDT performance based on competition between Type I and Type II against in vivo hypoxic solid tumors. This work pioneers a new strategy to implement type I PDT against solid hypoxic tumors using engineered MOFs.