Abstract
Antibiotic-resistant pathogens represent a significant global public health challenge, particularly in refractory infections associated with biofilms. Urgent development of innovative, safe, and therapeutically adaptive strategies to combat these resistant biofilms is essential. We present a novel biomimetic antibacterial system inspired by the multifunctional enzymatic properties of cerium-based metal-organic frameworks. This system utilizes the inherent oxidase and peroxidase activities of a nanozyme to generate reactive oxygen species (ROS) for bacterial eradication, while its phosphate-ester hydrolase activity disrupts bacterial genetic material and energy metabolism. By the reversible covalent binding between boronic acid groups and cis-diol groups on bacterial surfaces, combined with abundant cerium catalytic sites from the porous structure and the potent antibacterial effects of sanguinarine, we enhance targeted antibacterial activity. This system effectively penetrates extracellular polymeric substances (EPS) and demonstrates precise regulation of ROS, allowing for localized delivery of ROS and sanguinarine for biofilm eradication. Transcriptomic analyses indicate that this approach disrupts the cellular environment, impairs energy metabolism, inhibits bacterial attachment to EPS, and promotes biofilm dispersion by modulating drug resistance-related genes. In vivo experiments confirm that this nanocatalyst composite effectively treats biofilm-induced wounds with efficacy comparable to vancomycin, presenting a promising solution for managing chronic infections caused by antibiotic-resistant biofilms.