Dually Crosslinked Copper-Poly (Tannic Acid) Nanoparticles with Microenvironment-Responsiveness for Infected Wound Treatment.

Reducing the burden of death due to wound infection is an urgent global public health priority. Metal-phenolic networks (MPNs) receive widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and excellent antimicrobial properties brought about by polyphenols and metal ions. However, typical therapeutic MPNs show rapid release of metal ions due to their poor solution stability, impeding long-acting efficacy in multiple wound healing stages. To address these issues, we prepared copper-poly (tannic acid) nanoparticles (Cu-PTA NPs): robust (dually crosslinked), microenvironment-responsive, antibacterial, antioxidative and anti-inflammatory, which hierarchically modulate the infected wound healing process. Covalently polymerized via phenol-formaldehyde condensation and crosslinked with bioactive Cu 2+ , reactive polyphenols are preserved, and Cu 2+ are efficiently entrapped in the PTA scaffold. The proposed strategy relieves the systemic toxicity and only high ROS level as stimuli could "turn on" the catalytic activity of Cu 2+ to implement antibacterial therapy specifically in infected wound. Systematic tissue regeneration assessment on the infected full-thickness skin wounds of rats demonstrates enhanced wound healing rate. Cu-PTA NPs enables the direct application in infected wound and exertion of long-acting healing efficacy. This synergetic therapy strategies will further pave the way for more complicated infections and inflammatory diseases. This article is protected by copyright. All rights reserved.