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《工程(英文)》 >> 2021年 第7卷 第8期 doi: 10.1016/j.eng.2020.09.013

工程化仿生血小板膜包覆纳米颗粒阻断金黄色葡萄球菌的细胞毒性并防止致命的全身感染

a Division of Nephrology, Department of Internal Medicine & Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea
b Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea
c Division of Host–Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
d Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, USA
e Moores Cancer Center, University of California San Diego Health, La Jolla, CA 92037, USA
f Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA

收稿日期: 2020-06-26 修回日期: 2020-09-05 录用日期: 2020-09-07 发布日期: 2019-12-01

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摘要

金黄色葡萄球菌(S. aureus)是一种常见的人类病原体,它可以引发严重的侵袭性感染,如菌血症、败血症和心内膜炎,具有较高的发病率和死亡率。然而由于细菌的抗生素耐药性增强,如耐甲氧西林金黄色葡萄球菌(MRSA),加剧了此类细菌的发病率和死亡率。金黄色葡萄球菌的发病机制是由毒素的分泌推动的,如膜损伤孔α毒素,它有不同的细胞靶点,包括上皮细胞、内皮细胞、白细胞和血小板。本文采用人体血小板膜包覆纳米颗粒(PNP)作为一种仿生诱饵策略,来中和金黄色葡萄球菌的毒素,并维持宿主细胞的防御功能。血小板膜包覆纳米颗粒保护血小板免受由金黄色葡萄球菌毒素带来的损伤,维持血小板活化和杀菌活性。血小板膜包覆纳米颗粒也同样保护巨噬细胞免受由金黄色葡萄球菌毒素带来的损伤,支持巨噬细胞进行氧化迸发、产生一氧化氮和维持其杀菌活性,并减少耐甲氧西林金黄色葡萄球菌诱导的中性粒细胞胞外杀菌网络。在感染系统性耐甲氧西林金黄色葡萄球菌的小鼠模型中,血小板膜包覆纳米颗粒制剂减少了血液中的细菌数量并防止小鼠发生死亡。总之,目前的研究结果证明了血小板膜包覆纳米颗粒的治疗优点,如中和毒素、保护细胞和增加宿主对侵袭性金黄色葡萄球菌感染的抵抗力。

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