Zhao Chunzhen, Du Changxiao, Xu Jie, Zhao Yuqing, Shi Xiaoming, Zhang Dong, Zhang Xinmiao, Zhang Yi, Sun Han, Jiang Xixin, Du Zhen, Wang Mengjin, Xiao Meimei, Zang Mingwen
Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University 261053 Shandong PR China.
School of Pharmacy, Shandong Second Medical University Weifang 261053 Shandong PR China.
RSC Adv. 2025 Sep 1;15(38):31176-31193. doi: 10.1039/d5ra04493f. eCollection 2025 Aug 29.
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 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 HO. Specifically, under HO-deficient conditions, it catalyzes oxygen conversion to produce superoxide anions (O˙), while in HO-excess scenarios, it also depletes excessive HO 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 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.
与抗生素耐药性相关的挑战不断升级，在对抗微生物感染和预防生物膜形成的斗争中构成了巨大障碍。为应对这一挑战，我们开发了PEB-COP-Cu，这是一种低成本、易于获得的铜整合共价有机聚合物（COP），具有双酶样活性和内在光响应性，用于加速感染伤口愈合。这种材料是通过COF干凝胶（PEB-COP）的后金属化过程合成的，利用光活性四（4-氨基苯基）卟啉（TAPP）和β-酮烯胺，特别是1,3,5-三（3-二甲基氨基-1-氧代丙-2-烯基）苯（简称为TDOEB）作为基本构建单元，经过迈克尔加成消除反应得到。PEB-COP-Cu通过整合光热疗法（PTT）和I/II型光动力疗法（PDT）实现多模式抗菌作用，在有氧和缺氧环境中均能产生活性氧（ROS）。这种材料表现出双模拟酶活性（氧化酶和过氧化物酶），以实现有或无HO情况下ROS介导的细菌失活。具体而言，在HO缺乏条件下，它催化氧气转化产生超氧阴离子（O˙），而在HO过量的情况下，它还消耗过量的HO以增强˙OH的产生。这些酶促级联与PTT/PDT的协同整合建立了一个通过协调分子机制运作的综合抗菌系统。这种联合治疗策略展示了三重治疗优势，可有效根除细菌、抑制生物膜形成，并利用和调节感染微环境（IME）促进伤口愈合。我们的研究结果将PEB-COP-Cu确立为一个开创性的治疗平台，它同时解决了传统酶疗法的关键挑战，在将脱靶细胞毒性降至最低的同时显著提高了杀菌效果。
