Photoresponsive Cu-covalent organic polymer as multifunctional artificial enzyme for synergistic infected wound therapy

Abstract

The escalating challenges associated with antibiotic resistance have posed formidable obstacles in the fight against microbial infections and the prevention of biofilm formation. To address this challenge, we developed PEB-COP-Cu, a low-cost, readily available copper-integrated covalent organic polymer (COP) with dual enzyme-like activities and intrinsic photoresponsiveness, to accelerate infected wound healing. This material was synthesized through the post-metallization process of a COF xerogel (PEB-COP), obtained via a Michael addition elimination reaction, utilizing photoactive tetra-(4-aminophenyl)porphyrin (TAPP) and β-ketoenamine, specifically 1,3,5-tris(3-dimethylamino-1-oxoprop-2-en-yl)benzene (abbreviated as TDOEB), as the fundamental building blocks. PEB-COP-Cu enables multimodal antimicrobial action through integrated photothermal therapy (PTT) and type I/II photodynamic therapy (PDT), generating reactive oxygen species (ROS) in both oxygenated and hypoxic environments. This material demonstrates dual mimicking enzymatic activities (oxidase and peroxidase) to achieve ROS-mediated bacterial inactivation with or without H₂O₂. Specifically, under H₂O₂-deficient conditions, it catalyzes oxygen conversion to produce superoxide anions (O₂˙⁻), while in H₂O₂-excess scenarios, it also depletes excessive H₂O₂ to enhance ˙OH generation. The synergistic integration of these enzymatic cascades with PTT/PDT establishes a comprehensive antimicrobial system that operates through coordinated molecular mechanisms. This combined therapeutic strategy demonstrates threefold therapeutic advantages, which could effectively eradicate bacteria, inhibit biofilm formation, and promote wound healing via harnessing and modulating the infectious microenvironment (IME). Our findings establish PEB-COP-Cu as a pioneering therapeutic platform that simultaneously addresses the key challenges of conventional enzymatic therapy, achieving significantly improved biocidal efficacy while minimizing off-target cytotoxicity.