Bioinspired programmed antibiofilm strategies for accelerated wound healing via spatiotemporally controlled enzyme nanoreactors

Abstract

Biofilms, protected by their dense, self-produced matrix, pose a significant clinical challenge due to their antibiotic resistance, leading to persistent infections and delayed wound healing, particularly in diabetic patients. Tailored to the biofilm life cycle, a double-layered nanoreactor was developed for rapid and complete antibiofilm therapy. The inner layer, cross-linked with poly(allylamine hydrochloride) (PAH)/phosphate, dimeric indocyanine green (dICG), and bromothymol blue (BTB), shields glucose oxidase (GOx) and β-glucanase (β-DEX) from unfavorable environment. The outer layer is coated with bacteria-targeted gold nanozymes (AuNEs). The healing of biofilm-infected diabetic wounds progresses three spatiotemporal stages activated by light irradiation and pH changes. Initially, the photothermal effect of dICG triggers nitric oxide (NO)-mediated biofilm dispersion and lowers the wound pH via a GOx/AuNEs cascade reaction. The resulting acidic environment then induces nanoreactor disassembly, releasing β-DEX to degrade the biofilm matrix and facilitate deeper penetration. Finally, AuNEs specifically recognize and eliminate planktonic bacteria, further disrupting the biofilms and accelerating wound healing by generating reactive oxygen species (ROS) and more toxic reactive nitrogen species (RNS). The wound status can be monitored in real-time using BTB's colorimetric pH analysis for visual feedback on treatment progress. This multifunctional design offers a programmed antibiofilm strategy for dynamic wound management.