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

作者：Jianxiong Dou, Weilong Shang, Huagang Peng, Yi Yang, Juan Chen, Yifan Rao, Li Tan, Zhen Hu, Yuting Wang, Xiaonan Huang, Yuhua Yang, Jianghong Wu, Qiwen Hu, Chuan Xiao, Xiancai Rao · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s524445 · 被引用次数：2 · 研究领域：Bacterial Infections and Vaccines、Pneumocystis jirovecii pneumonia detection and treatment、Pneumonia and Respiratory Infections

Introduction: Methicillin-resistant Staphylococcus aureus (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 ( ΔagrA MVs) derived from the attenuated S. aureus strain RN4220Δ agrA , generating VAN-loaded nanoparticles ( ΔagrA MV-VAN). In vitro and in vivo experiments were performed to test the efficacy of ΔagrA MV-VAN in intracellular MRSA clearance. Results: ΔagrA MV-VAN demonstrated sustained VAN release and efficient extracellular MRSA eradication. Moreover, macrophages actively internalized ΔagrA MV-VAN, leading to VAN accumulation in intracellular compartments and M1 macrophage polarization, which increased MRSA killing. In vivo animal experiments revealed that ΔagrA 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. Keywords: MRSA, ΔagrA MV-VAN nanoparticles, macrophage activation, intracellular infections, intracellularly bacterial clearance