Polymersomes Eradicating Intracellular Bacteria
Polymersomes Eradicating Intracellular Bacteria
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DOI：
10.1021/acsnano.0c01870
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发表时间：
2020-07-28
期刊：
影响因子：
17.1
通讯作者：
Rizzello, Loris
中科院分区：
文献类型：
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作者：
Fenaroli, Federico;Robertson, James D.;Rizzello, Loris
单核细胞吞噬细胞如单核细胞、组织特异性巨噬细胞和树突细胞是先天性和适应性免疫中的主要作用者。这些专职吞噬细胞可以被细胞内细菌寄生，使它们从管家变成藏身之处，并有利于慢性和/或播散性感染。其中最臭名昭著的是导致结核病（TB）的细菌，结核病是最流行和最致命的疾病之一，世界三分之一的人口受到感染，全球平均每年有180万人死亡。在这里，我们证明了有效的靶向和细胞内交付的抗生素感染的巨噬细胞在体外和体内，使用pH敏感的纳米聚合物囊泡制成的PMPC-PDPA嵌段共聚物。多聚体显示出显著增强抗生素杀死牛分枝杆菌、结核分枝杆菌和另一种已建立的细胞内病原体金黄色葡萄球菌的功效的能力。此外，他们在斑马鱼模型中证明了很容易进入结核样肉芽肿组织-最苛刻的渗透环境之一。因此，我们成功地利用这种靶向有效根除了几种细胞内细菌，包括M。结核病是人类结核病的病原体。
Mononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world's population infected and an average of 1.8 million deaths/year worldwide. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to infected macrophages both in vitro and in vivo, using pH-sensitive nanoscopic polymersomes made of PMPC-PDPA block copolymer. Polymersomes showed the ability to significantly enhance the efficacy of the antibiotics killing Mycobacterium bovis, Mycobacterium tuberculosis, and another established intracellular pathogen, Staphylococcus aureus. Moreover, they demonstrated to easily access TB-like granuloma tissues-one of the harshest environments to penetrate-in zebrafish models. We thus successfully exploited this targeting for the effective eradication of several intracellular bacteria, including M. tuberculosis, the etiological agent of human TB.