Photogenerated Radical Amplified D–A–D Metal‐Covalent Organic Frameworks for Highly Efficient Photodynamic Tumor Therapy

Abstract

Abstract While metal covalent organic frameworks (MCOFs) possess excellent optical properties and electron transport capabilities, their performance in antitumor therapy is hampered by limited compositional diversity. This constraint impedes the nonradiative relaxation of excited states and reduces the efficiency of reactive oxygen species (ROS) generation. Here, we rationally designed a tri‐component electron donor–acceptor–donator (D–A–D) type MCOFs (CuTD‐COF). Compared to the two‐component D–A type MCOFs (CuT‐COF), CuTD‐COF exhibits an extended excited‐state lifetime, enhanced light‐harvesting capability due to its narrow band gap, and intensified photoradical effects, thereby achieving potent tumor suppression. Mechanistically, the D–A–D structured CuTD‐COF utilizes multiple electron‐transfer pathways. These enhance intra‐layer charge transport, reduce exciton binding energies, accelerate photogenerated carrier separation/migration, and suppress charge recombination, collectively boosting ROS generation. This yields potent photodynamic cytotoxicity in vitro and outstanding antitumor efficacy in HCT116 xenografts. Combined experimental and DFT studies reveal that distinct exciton behavior in regulating ROS generation between two D–A–D MCOFs stems from their divergent band energetics and O 2 adsorption energies. This work not only diversifies photoelectronic architectures in MCOFs but also advances cancer phototherapy development.