Bacterial Microenvironment-Responsive Fe-Ce6 Nanoparticles Accelerate Infected Wound Healing via In Situ Generation of Nanozyme and Photodynamic Antibacterial Activity
Bacterial infection remains a critical impediment in clinical wound management, with conventional antibiotic therapies compromised by cytotoxicity and escalating drug resistance. Existing photodynamic therapy (PDT) and nanozyme-based antibacterial strategies often lack microenvironment specificity, exhibiting persistent activity that risks collateral tissue damage. This study reports the development of bacterial microenvironment-responsive Fe-Ce6 nanoparticles (NPs) that enable in situ generation of peroxidase (POD)-like activity and PDT activation for enhanced antibacterial wound therapy. Under stimulation by bacteria-secreted adenosine triphosphate (ATP), Fe-Ce6 NPs undergo disassembly and in situ formation of Fe-ATP complexes, synchronously releasing the Ce6 photosensitizer. The Fe-ATP complex, possessing POD-like activity, catalyzes the conversion of hydrogen peroxide (H2O2) into hydroxyl radicals (·OH), while Ce6 generates singlet oxygen (1O2) under 671 nm laser irradiation, synergistically augmenting nanozyme-PDT antibacterial effects. Intracellular ATP released from lysed bacteria further amplifies this cascade, promoting Fe-ATP complex formation and Ce6 release, ultimately inducing an avalanche effect that efficiently kills bacteria and reinforces therapeutic action. In vitro, the system demonstrates remarkable antibacterial activity against Staphylococcus aureus and Escherichia coli in simulated bacterial environments. In vivo, it exhibits substantial bactericidal efficacy and accelerates wound healing. This study presents the Fe-Ce6 NPs smart system activated by bacterial microenvironments via an off-on mechanism, enabling precise reactive oxygen species (ROS) generation control, significantly reducing non-target tissue damage associated with traditional therapies, and offering a novel paradigm for developing microenvironment-responsive intelligent antibacterial systems.