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《工程(英文)》 >> 2022年 第15卷 第8期 doi: 10.1016/j.eng.2021.12.021

用于精准和响应性治疗胞质耐药菌的刚性药物递送系统

a National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
b Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China

收稿日期: 2022-07-13 修回日期: 2021-09-26 录用日期: 2021-12-24 发布日期: 2022-04-12

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摘要

随着细菌耐药性的快速出现和广泛传播,导致抗菌药物对致命性细菌病原体的疗效逐渐降低。目前新型抗菌药物的发现和开发进展十分缓慢,因此迫切需要新的治疗策略来对抗多重耐药(multidrug-resistant, MDR)细菌,尤其是宿主细胞中的病原菌。功能性纳米颗粒作为细胞内药物递送系统具有良好发展潜力,主要优点为高生物相容性和可调节的表面修饰。基于纳米颗粒刚性可增强细胞摄取,制备了涂有细菌响应性磷脂的刚性功能化纳米颗粒(rigidity-functionalized nanoparticles, RFN)以促进内吞作用,从而增加细胞内抗菌药物累积。以耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)和致病性蜡样芽孢杆菌为模型,RFN在4 h 内清除了99%的MDR细菌,证明了其精准递送和高抗菌疗效。另外,通过改变表面的磷脂成分来调节静电效应,实现了RFN精准靶向溶酶体和重新编程其在细胞内分布。最后,RFN在由MRSA引起的伤口感染和菌血症动物模型中显示出高疗效。综上所述,本研究提供了一个易于调控的刚性递送系统,该系统具有响应释放特性,并且通过抗菌药物胞内重分布提升抗菌疗效,为未来针对胞质细菌感染的精准治疗提供新思路。

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