Tetrazine-enhanced donor-acceptor-donor metal-organic frameworks for photodynamic antibacterial therapy and wound healing
Yanzhao Chen, Yangyin Xue, Xiaowei Xu, Yu Su, Xidan Tong, Long Zhu, Yifei Zuo, Chao Ban, Jiaxuan Chen, Wancai Que, Yueqin Zheng, Weiwei Guo
Abstract
Multidrug-resistant infections and impaired healing in chronic diabetic wounds are major clinical challenges. Photodynamic therapy (PDT) is a promising alternative, but its efficacy is limited by conventional photosensitizers. Here, we design two donor-acceptor-donor (D-A-D) metal-organic frameworks (MOFs) using a tetrazine core to narrow the band gap, which enhances visible-light-driven reactive oxygen species (ROS) generation. These MOFs exhibit superior photocatalytic antibacterial activity over benchmark materials. After functionalization with L-arginine, the resulting composites (e.g., A@Zn-TDP) co-release ROS, nitric oxide (NO), and reactive nitrogen species (RNS) enabling rapid and broad-spectrum bacterial eradication (including against MRSA) at low concentrations (25 μg/mL) while accelerating tissue regeneration. In a male diabetic mouse model, A@Zn-TDP treatment under light reduces bacterial load by >95%, controls inflammation, promotes angiogenesis, and speeds up wound closure. This study establishes tetrazine-based D-A-D MOFs as a rationally designed platform for effective PDT and wound healing, underscoring their clinical translational potential. Photodynamic therapy is limited by inefficient photosensitizers. Here, Chen et al. develop tetrazine-enhanced donor-acceptor-donor metal-organic frameworks to enhance photocatalytic ROS generation for broad-spectrum antibacterial activity and accelerated healing of infected diabetic wounds.