Bifunctional Metal–Organic Frameworks Integrate Energy‐ and Electron‐Transfer Pathways for Enhanced Photodynamic Therapy

ABSTRACT Metal–organic frameworks (MOFs) have emerged as promising nanophotosensitizers for photodynamic therapy (PDT), but most reported systems rely predominantly on a single O 2 ‐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 (VIO 2+ ) 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 VIO 2+ to generate viologen radical species, which mediate O 2 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 O 2 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.