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  3. Photoactive metal-covalent organic framework nanozymes with enhanced peroxidase-mimicking activity for eliminating drug-resistant bacterial infections

Photoactive metal-covalent organic framework nanozymes with enhanced peroxidase-mimicking activity for eliminating drug-resistant bacterial infections

  • J Colloid Interface Sci. 2025 Jun 12;699(Pt 1):138178. doi: 10.1016/j.jcis.2025.138178.
Taju Wu 1,  Fang Han 2,  Jinpei Mei 3,  Jie Chen 3,  Panpan Li 4,  Mengyi Li 4,  Jiaxin Shen 2,  Xue Han 1,  Rentian Song 5,  Sainan Hou 5,  Xinyu Li 6,  Yutian Su 7,  Wei Yue 8,  Baohong Sun 9
Affiliations

Affiliations

  • 1 School of Life Science, Bengbu Medical University, Bengbu 233030, PR China; Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu 233030, PR China.
  • 2 Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu 233030, PR China.
  • 3 Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu 233030, PR China; Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, School of Pharmacy, Bengbu Medical University, Bengbu 233030, PR China.
  • 4 Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, School of Pharmacy, Bengbu Medical University, Bengbu 233030, PR China.
  • 5 School of Life Science, Bengbu Medical University, Bengbu 233030, PR China.
  • 6 Department of Animal Science, College of Animal Science, Hebei North University, Zhangjiakou 075000, PR China.
  • 7 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou 510120, PR China. Electronic address: 2023390241@gzhmu.edu.cn.
  • 8 Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu 233030, PR China. Electronic address: yuewei@bbmu.edu.cn.
  • 9 Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu 233030, PR China; Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, School of Pharmacy, Bengbu Medical University, Bengbu 233030, PR China. Electronic address: baohongsun7@bbmu.edu.cn.
PMID: 40527142 DOI: 10.1016/j.jcis.2025.138178
Abstract

Nanozyme-mediated Ferroptosis strategies present a promising approach for eliminating clinically prevalent superbugs. However, the catalytic efficiency of conventional nanozymes is frequently limited by pH variations and can lead to sustained substrate depletion, potentially inducing tissue inflammation. In this study, we introduce a photoactive copper-metalized single-atom covalent organic framework (CuSA-COF) nanozyme designed to efficiently initiate a nonferrous ferroptosis-like mechanism within Bacterial cells. CuSA-COF is synthesized by integrating a photoconductive porphyrin framework with o-phenanthroline ligands, subsequently coordinating monoatomically dispersed copper. Upon light irradiation, CuSA-COF swiftly produces singlet oxygen, hydroxyl radicals, and protons via a combination of Type II photodynamic and photo-Fenton reactions. This metal-protonation approach creates an acidic microenvironment that augments the peroxidase-like activity of CuSA-COF towards hydrogen peroxide. Consequently, CuSA-COF induces a swift intracellular Reactive Oxygen Species surge, encourages glutathione depletion-mediated Glutathione Peroxidase 4 inactivation, and disrupts metabolic pathways, ultimately leading to lipid peroxidation-driven ferroptotic damage. This ferroptosis-inducing nanozyme demonstrates potent Antibacterial activity against both gram-positive and gram-negative bacteria, including clinically isolated methicillin-resistant Staphylococcus aureus and its biofilms. The precisely engineered Bacterial ferroptosis-like mechanism proposed herein may offer new insights into the treatment of drug-resistant Bacterial infections.

Keywords

Covalent organic frameworks; Drug-resistance bacteria; Ferroptosis-like mechanism; Nanozymes; Wound healing.

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