Gram‐Positive Bacteria Cell Wall Driven Self‐Disassembled Nanovesicles against Methicillin‐Resistant Staphylococcus Aureus

Abstract

AbstractIn the delivery system, high‐performance targeting and local burst‐releasing of antibiotics enable the enhancement of antipathogen efficacy and reduction of drug‐resistance risk. Bacteria cell wall driven self‐disassembled nanovesicles (BSNs) composed of a dense H‐aggregated cyanine bilayer are herein reported. The nanovesicle displays the trigger‐disassembly and turn‐on near infrared (NIR) fluorescence property activated by Gram‐positive bacteria. Mechanistic studies indicate that the interaction between nanovesicles and lipoteinchoic acid within the bacterial cell wall disrupts nanovesicles and the free cyanine molecules insert into the network of peptidoglycan, which brings recovered fluorescence. Meanwhile, owing to the burst release of the oritavancin antibiotic payload inside the nanovesicle, the minimum inhibitory concentration of oritavancin is significantly reduced by fourfold compared to that of the free one. Intriguingly, this smart nanoantibiotic effectively enhances the defense against methicillin‐resistant Staphylococcus aureus both in vitro and in vivo, meanwhile the NIR fluorescence signal enables quantitative bioimaging of the therapuetic outcome.