Vancomycin-Loaded Isogenous Membrane Vesicles for Macrophage Activation and Intracellular Methicillin-Resistant Elimination.

INTRODUCTION

Methicillin-resistant (MRSA), a notorious multidrug-resistant (MDR) pathogen, frequently resides and proliferates within macrophages, contributing to refractory and recurrent infections. Conventional antibiotics exhibit limited efficacy against intracellular MRSA due to poor cellular penetration.

METHODS

Vancomycin (VAN) was encapsulated into membrane vesicles (MVs) derived from the attenuated strain RN4220Δ, generating VAN-loaded nanoparticles (MV-VAN). In vitro and in vivo experiments were performed to test the efficacy of MV-VAN in intracellular MRSA clearance.

RESULTS

MV-VAN demonstrated sustained VAN release and efficient extracellular MRSA eradication. Moreover, macrophages actively internalized MV-VAN, leading to VAN accumulation in intracellular compartments and M1 macrophage polarization, which increased MRSA killing. In vivo animal experiments revealed that MV-VAN was safe and effectively eliminated intracellular MRSA in abdominal infections.

CONCLUSION

Our findings propose a nanotherapeutic strategy that uses bacterial-derived vesicles for targeted antibiotic delivery, overcoming the intrinsic limitations of conventional therapies against intracellular MDR pathogens.