Large‐Pore 3D Covalent Organic Frameworks with Light‐Sensitized Synergy for Efficient Photocatalytic Antibacterial Therapies and Wound Healing

Escalating antimicrobial resistance and declining antibiotic efficacy spur interest in photocatalytic antibacterial therapies. Covalent organic frameworks (COFs) are promising photodynamic antibacterial agents, though rapid carrier recombination, low reactive oxygen species (ROS) yields, and poor photostability remain constraints. Herein, we report the successful synthesis of two large‐pore [8+2] 3D‐bcu‐COFs. SEU‐301 was constructed from an 8‐connected porphyrin building unit and a linear tetraphenyl linker. Introducing a linear side‐chain bis(benzothiadiazole) linker via three‐component functional modulation afforded SEU‐302, which enhances light absorption, accelerates charge separation, and suppresses carrier recombination, thereby extending the excited‐state lifetime—confirmed by femtosecond transient absorption spectroscopy (fs‐TAS) and density functional theory (DFT) calculations. Further proteomic analysis shows that the ROS efficiently generated by light‐activated SEU‐302 elicit membrane damage and homeostatic imbalance, precipitating a cascade of stress responses that culminate in metabolic dysregulation, while also synergistically combating bacteria and inflammation. The therapeutic potential was further validated in vitro and in vivo, where light‐activated SEU‐302 not only effectively eliminated Staphylococcus aureus and inhibited its proliferation, but also promoted wound healing with increased collagen deposition and hair follicle regeneration. Results identify 3D COFs as very promising materials for both photodynamic therapies and antibacterial therapies.