Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia 作者:Fangyu Zhang, Jia Zhuang, Zhengxing Li, Hua Gong, Berta Esteban-Fernández de ávila, Yaou Duan, Qiangzhe Zhang, Jiarong Zhou, Lu Yin, Emil Karshalev, Weiwei Gao, Victor Nizet, et al. 查看更多 期刊:Nature Materials 發(fā)表時(shí)間:2022/09/22 數(shù)字識(shí)別碼:10.1038/s41563-022-01360-9 摘要: 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?1) 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. 銅綠假單胞菌引起的肺炎常常致命。假如通過(guò)靜脈注射抗生素進(jìn)行治療,有時(shí)只有很小一部分藥物會(huì)進(jìn)入肺部,治療效果不佳,病情嚴(yán)重的患者死亡率很高。最近,在一項(xiàng)發(fā)表于《自然·材料》的研究中,科學(xué)家開(kāi)發(fā)出一種微型機(jī)器人,在患有這種細(xì)菌性肺炎的小鼠體內(nèi)輸送抗生素,使存活率高達(dá)100%。 研究團(tuán)隊(duì)設(shè)計(jì)的微型機(jī)器人由藻類(lèi)細(xì)胞制成,表面覆蓋著抗生素填充的納米顆粒。藻類(lèi)細(xì)胞讓機(jī)器人能夠四處游動(dòng),將抗生素輸送給肺部的更多細(xì)菌。含有抗生素的納米顆粒由微小的、可生物降解的聚合物球體制成,球體上涂有中性粒細(xì)胞的細(xì)胞膜,這些膜能夠中和細(xì)菌與機(jī)體免疫系統(tǒng)自身產(chǎn)生的炎癥分子,有助于減少炎癥,對(duì)抗肺部感染??茖W(xué)家用這樣的微型機(jī)器人來(lái)治療銅綠假單胞菌引起急性肺部感染的小鼠,這些機(jī)器人被輸送到小鼠肺部一周后已將感染完全清除。所有接受治療的小鼠都存活了30天以上,而未經(jīng)治療的小鼠則在3天內(nèi)死亡。研究者還提到,治療后身體能夠消化掉藻類(lèi)和剩余的納米顆粒,不會(huì)留下有毒物質(zhì)。
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