Yuan Pingping, Zhou Shijie, Li Qianqian, Li Lin, Qu Shaoqi
College of Veterinary Medicine, Anhui Agricultural University, Hefei, 230036, China.
Center for the Creation and Evaluation of New Veterinary Drugs, Anhui Agricultural University, Hefei, 230036, China.
Synth Syst Biotechnol. 2025 Jul 3;10(4):1200-1207. doi: 10.1016/j.synbio.2025.07.001. eCollection 2025 Dec.
Bacterial infections pose a major threat to human health and economic stability. In particular, intracellular bacterial infections present significant clinical challenges due to antibiotic resistance and poor drug penetration. Therefore, there is an urgent need to develop novel therapeutic strategies to address the problem of intracellular bacterial infections. Extracellular bacterial vesicles become ideal delivery systems due to their natural targeting properties. Here, we developed a bacteria-derived extracellular vesicles (EVs)-based drug delivery platform to enhance the therapeutic efficacy of antibiotics against intracellular infections. EVs were successfully isolated and increased production from by ultracentrifugation, then loaded with ceftiofur (CEF) via co-incubation. tests demonstrated the potent antibacterial activity of CEF, achieving complete growth inhibition within 24 h and a 4-log viability reduction in 4 h. Furthermore, confocal microscopy revealed efficient CEV internalization in IEC-6 cells, with 12-fold greater intracellular bacterial clearance than free CEF. , CEV-incorporated hydrogel (CEVH) significantly reduced both intra- and extracellular bacterial loads and accelerated wound healing. These findings demonstrate that bacterial EVs serve as a universal delivery platform to significantly enhance the efficacy of existing antibiotics against intracellular infections.
细菌感染对人类健康和经济稳定构成重大威胁。特别是，由于抗生素耐药性和药物渗透性差，细胞内细菌感染带来了重大的临床挑战。因此，迫切需要开发新的治疗策略来解决细胞内细菌感染问题。细胞外细菌囊泡因其天然的靶向特性而成为理想的递送系统。在此，我们开发了一种基于细菌衍生的细胞外囊泡（EVs）的药物递送平台，以提高抗生素对细胞内感染的治疗效果。通过超速离心成功分离并增加了EVs的产量，然后通过共孵育加载头孢噻呋（CEF）。测试证明了CEF具有强大的抗菌活性，在24小时内实现完全生长抑制，4小时内活菌数量减少4个对数级。此外，共聚焦显微镜显示CEV在IEC-6细胞中有效内化，细胞内细菌清除率比游离CEF高12倍。含CEV的水凝胶（CEVH）显著降低了细胞内和细胞外的细菌载量，并加速了伤口愈合。这些发现表明，细菌EVs作为一种通用的递送平台，可显著提高现有抗生素对细胞内感染的疗效。
