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 () and Weiwei Guo ()
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Yanzhao Chen: China Pharmaceutical University, School of Science
Yangyin Xue: China Pharmaceutical University, School of Science
Xiaowei Xu: China Pharmaceutical University, School of Science
Yu Su: China Pharmaceutical University, School of Science
Xidan Tong: China Pharmaceutical University, School of Science
Long Zhu: China Pharmaceutical University, School of Science
Yifei Zuo: China Pharmaceutical University, School of Science
Chao Ban: China Pharmaceutical University, School of Science
Jiaxuan Chen: China Pharmaceutical University, School of Science
Wancai Que: Fujian Medical University Union Hospital, Phase I Clinical Trial Unit
Yueqin Zheng: China Pharmaceutical University, Center of Drug Discovery, State Key Laboratory of Natural Medicine
Weiwei Guo: China Pharmaceutical University, School of Science

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-65527-z

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