Bifunctional Metal-Organic Frameworks Integrate Energy- and Electron-Transfer Pathways for Enhanced Photodynamic Therapy.

Metal-organic frameworks (MOFs) have emerged as promising nanophotosensitizers for photodynamic therapy (PDT), but most reported systems rely predominantly on a single O2-activation pathway, limiting their ability to produce complementary reactive oxygen species (ROS). Herein, we report a bifunctional MOF, Hf-VIO-DBP, that integrates porphyrinic photosensitizers (DBP) and viologen electron mediators (VIO2+) within a single framework to establish a dual-channel photoactive platform. The close spatial proximity of these two functional units enables efficient intra-framework electron transfer while preserving the energy transfer capability of the porphyrinic photosensitizers. Upon 630 nm irradiation, excited DBP transfers electrons to VIO2+ to generate viologen radical species, which mediate O2 reduction to generate type I ROS, including superoxide, hydrogen peroxide, and hydroxyl radicals. The resulting DBP radical cation is reduced by endogenous biomolecules such as 1,4-dihydronicotinamide adenine dinucleotide, thereby regenerating DBP and sustaining the photoredox cycle. Concurrently, energy transfer from excited DBP to O2 produces singlet oxygen through a type II pathway. Compared with the viologen-free MOF analogue, Hf-VIO-DBP markedly enhances type I ROS generation while retaining efficient type II ROS production, resulting in substantially improved overall ROS yields and phototoxicity. Therefore, Hf-VIO-DBP achieves potent PDT efficacy in CT26 and MC38 murine colon cancer models.