Misuse of antibiotics leads to the emergence of multidrug-resistant (MDR) bacterial infection globally. Vancomycin (V), the so-called last line defense against methicillin resistance Staphylococcus aureus (MRSA), declines its therapeutic effect each year due to high-level of resistance. Stewardships, drug-combination, development of antibiotic delivery and biomimetic systems are the current practical strategies to reduce the resistance emergence. In this study, red blood cell membrane (RBCM) and bacterial exotoxins-responsive supramolecular gelatin nanoparticles (SGNPs) loading vancomycin and chlorogenic acid (C) are used to construct the VC-SGNPs-R drug delivery system to inhibit MRSA infection both in vitro and in vivo. RBCM coating evade the immune system, prolong circulation and neutralize exotoxins in an infection-microenvironment. Moreover, excellent in vivo inflammation healing, wound repairing and MRSA eradication were confirmed by leg and skin infection mice model. The intense fluorescence molecular tomography (FMT) measurement of VC-SGNPs-R, tissue quantification and successful wound healing shows its capability for on-demand antibiotic delivery and responsiveness in an infection-microenvironment.

This approach develops a biomimetic drug delivery system of VC-SGNPs-R with long circulation and synergistic effect against MDR bacteria.