Tetrazine-enhanced donor-acceptor-donor metal-organic frameworks for photodynamic antibacterial therapy and wound healing.

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.