Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment

Abstract

AbstractDrug‐resistant bacterial infections and their lipopolysaccharide‐related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R‐DPB‐TA‐Ce). The design involves the fusion of end‐terminal lipidated polypeptides containing side‐chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R‐DPB), followed by coordination with the tannic acid‐cerium complex (TA‐Ce) to assemble into a biomimetic nanonet through boronic acid‐polyphenol‐metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R‐DPB‐TA‐Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement‐enhanced multiple interactions based on the boronic acid–polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R‐DPB‐TA‐Ce as a new biomimetic assembled drug delivery system in antibacterial, anti‐inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.