Bacteria-Targeted Single-Atom Nanozyme With Photothermal-Augmented Multi-Enzymatic Cascade and NO Delivery for Enhanced Infected Wound Healing
Junyang Chen, Qing Chen, Xudong Qin, Haixia Yang, Xin Wang, Jianliang Zhou, Ying-Wei Yang, Jian Tian
Advanced Science 2025
https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202509621
Abstract
Infected diabetic wound management confronts significant challenges, including bacterial resistance, oxidative stress, and impaired vascular repair, resulting in substantial unmet clinical needs. To address these issues, a multifunctional therapeutic nanoplatform, mCu-SAE@BNN6@PEG-Van (CBPV), is developed by sequentially functionalizing mesoporous copper single-atom nanozymes (mCu-SAE) loaded with the nitric oxide (NO) donor BNN6 and vancomycin-conjugated polyethylene glycol (PEG-Van). CBPV integrates three synergistic therapeutic modalities: 1) pathogen-specific targeting via Van-mediated bacterial recognition; 2) NIR-II photothermally enhanced catalytic therapy via Cu-N3 centers in mCu-SAE, generating reactive oxygen species; 3) photoactivated NO release from BNN6, enabling peroxynitrite (ONOO−) formation through radical coupling. Irradiation of CBPV with a 1064-nm laser simultaneously enables deep-tissue photothermal activation, thermally boosted chemodynamic activity, and controlled NO liberation. In vitro and in vivo studies demonstrate that CBPV exhibits remarkable antibiofilm activity and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (99.6% inactivation) while promoting angiogenesis through NO-mediated endothelial cell activation. Both epidermal wound and subcutaneous cyst models show accelerated healing with enhanced collagen deposition and neovascularization. By integrating bacterial targeting with NIR-II-responsive therapeutic cascades, this work establishes a spatiotemporally controlled therapeutic paradigm that simultaneously addresses infection control and tissue regeneration in chronic wounds, offering a promising translational strategy for managing complex diabetic wounds.
