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纳米颗粒修饰的微机器人用于体内抗生素递送治疗急性细菌性肺炎。

Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia.

机构信息

Department of NanoEngineering and Chemical Engineering Program, University of California San Diego, La Jolla, CA, USA.

Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.

出版信息

Nat Mater. 2022 Nov;21(11):1324-1332. doi: 10.1038/s41563-022-01360-9. Epub 2022 Sep 22.

Abstract

Bioinspired microrobots capable of actively moving in biological fluids have attracted considerable attention for biomedical applications because of their unique dynamic features that are otherwise difficult to achieve by their static counterparts. Here we use click chemistry to attach antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles to natural microalgae, thus creating hybrid microrobots for the active delivery of antibiotics in the lungs in vivo. The microrobots show fast speed (>110 µm s) in simulated lung fluid and uniform distribution into deep lung tissues, low clearance by alveolar macrophages and superb tissue retention time (>2 days) after intratracheal administration to test animals. In a mouse model of acute Pseudomonas aeruginosa pneumonia, the microrobots effectively reduce bacterial burden and substantially lessen animal mortality, with negligible toxicity. Overall, these findings highlight the attractive functions of algae-nanoparticle hybrid microrobots for the active in vivo delivery of therapeutics to the lungs in intensive care unit settings.

摘要

受生物启发的能够在生物流体中主动移动的微型机器人因其独特的动态特性而引起了人们对生物医学应用的极大关注,这些动态特性是其静态对应物难以实现的。在这里,我们使用点击化学将载有抗生素的中性粒细胞膜包被的聚合物纳米颗粒附着到天然微藻上,从而创造出用于在体内肺部主动输送抗生素的混合微型机器人。这些微型机器人在模拟的肺液中表现出较快的速度(>110μm/s)和均匀分布到深层肺组织的能力,在经气管给予试验动物后,它们被肺泡巨噬细胞清除的程度较低,并且具有极好的组织保留时间(>2 天)。在急性铜绿假单胞菌肺炎的小鼠模型中,这些微型机器人有效地降低了细菌负荷并大大降低了动物死亡率,而且毒性可忽略不计。总体而言,这些发现突出了藻类-纳米颗粒混合微型机器人在重症监护环境下主动向肺部输送治疗药物的有吸引力的功能。

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