A bacteria-responsive nanoplatform with biofilm dispersion and ROS scavenging for the healing of infected diabetic wounds

Abstract

Delayed wound healing in patients with diabetes remains a major health challenge worldwide. Uncontrolled bacterial infection leads to excessive production of reactive oxygen species (ROS) and persistent inflammatory responses, which seriously hinder conventional physiological healing processes after injury. Biofilms, as protective barriers for bacteria, pose a critical obstacle to effective bacterial eradication. Herein, an innovative therapeutic nanoplatform with in situ antibacterial and antioxidant properties is developed for enhancing infected diabetic wound healing. The enrichment of phenylboronic acid (PBA) moieties on the nanoplatform enhances biofilm penetration, actively anchors and aggregates the enclosed bacteria through the "multivalent effect", with an anchoring efficiency as high as 80 %. Additionally, glycine moieties on the nanoplatform ensure spatial extensibility by charge repulsion, enabling targeted antibiotic release around bacteria. This precise antibacterial effect increases the bactericidal activities of the nanoplatform against S. aureus or P. aeruginosa by 25 % and 22 % respectively, effectively eliminating the bacteria and dispersing the biofilms. Furthermore, 3,4-dihydropyrimidin-2(1H)-one (DHPM) moieties act as ROS scavengers that alleviate oxidative stress and inflammatory responses, promoting tissue repair progression into the proliferative phase characterized by increased extracellular matrix deposition, angiogenesis, and granulation tissue formation, ultimately accelerating diabetic wound healing. Overall, this work presents an innovative bacterial response strategy for achieving in situ antibacterial and antioxidant effects in infected tissues and provides a promising therapeutic approach for treating infected diabetic wounds. STATEMENT OF SIGNIFICANCE: Infected diabetic wound management remains a major world health issue. Severe bacterial infection leads to excessive oxidative stress and persistent inflammatory response, which seriously hinders the wound healing process. As a protective barrier for bacteria, biofilms are a key obstacle to effective bacterial clearance. This study provides a bacteria-responsive nanoplatform for the healing of infected diabetic wounds. The nanoplatform not only exhibits improved biofilm penetration but also actively anchors the enclosed bacteria and enables targeted antibiotic release to disperse the biofilm. The DHPM moieties of the nanoplatform act as ROS scavengers which could alleviate inflammatory responses, promote tissue repair progression into the proliferative phase, and ultimately accelerate diabetic wound repair.

Keywords: Bacteria-responsive nanoplatform; Biofilm dispersion; In situ ros scavenging; Infected diabetic wounds; Targeted antibiotic release.