Smart Nanosilver Strikes Twice: Precision Bacteria Killing Meets Autophagy‐Boosted Healing for Infected Wounds
Jiaojiao Zhu, Qingya Zeng, Yutian Liu, Yilan Lin, Ding Ma, Tiao Wen, Pei Li, Wenhu Zhou
Abstract
Abstract Effective management of infected chronic wounds requires innovative strategies that combine precise antibacterial action with microenvironment reprogramming. Here, a pH‐responsive core‐shell nanosilver platform (PST/Ag) is reported that exploits structural disparities between bacterial and mammalian cells to achieve dual therapeutic effects. The PST/Ag selectively adheres to bacterial membranes and rapidly releases Ag + via pH‐responsive dissolution in the acidic infection niche, achieving multimodal bactericidal effects while mitigating resistance risks. Crucially, PST/Ag minimizes off‐target toxicity through disparity‐driven cellular trafficking: reduced endocytosis in skin cells confines Ag + release within lysosomal compartments, where Ag + is dynamically reduced to secondary nanoparticles, ensuring sustained sub‐toxic Ag + flux. This controlled release triggers a Hormesis effect—low‐dose Ag + activates protective autophagy, synergizing with polyserotonin shell‐derived metabolites to enhance fibroblast migration, angiogenesis, and extracellular matrix remodeling. In murine‐infected wound and rabbit wound models, PST/Ag outperforms conventional silver nanoparticles by concurrently eradicating bacteria, accelerating re‐epithelialization, and preventing scar formation. This “defense‐regulation” dual modality—precision antibacterial coupled with microenvironment reprogramming—redefines nanosilver‐based wound management paradigms, offering a translatable solution for complex tissue repair.