利用低氧反应纳米颗粒精确给药抗生素和增强剂克服革兰氏阴性菌的抗生素耐药性

IF 5.2 Q1 POLYMER SCIENCE
Weiguang Bai, Yongjin Hu, Jinghua Zhao, Liuqi Shi, Chunhua Ge, Zhiyuan Zhu and Jingyi Rao*, 
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引用次数: 0

摘要

抗生素,特别是针对与外膜相关的固有耐药革兰氏阴性病原体的发展停滞,导致全球出现新的抗生素危机。为了给现有药物注入活力,我们在此报道了一种低氧反应纳米颗粒(NP),它包裹了一种疏水抗生素利福平和一种阳离子增强剂聚砜。抗生素和增强剂的同时释放可以根据细菌引起的缺氧的严重程度进行促进和抑制,从而精确地给药。在具有膜破坏能力的多磺酸的协同作用下,NPs在消除浮游革兰氏阴性P. aeruginosa细菌方面可以大量减少抗生素剂量高达66-95%,在利福平MIC下,成熟生物膜中的细菌减少了8倍。NP配方表明,由缺氧调节的抗生素和增强剂的精确剂量为治疗革兰氏阴性细菌感染提供了一种有希望的策略,可以最大限度地提高疗效并减少毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria

Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria

The stalling development of antibiotics, especially against intrinsically resistant Gram-negative pathogens associated with outer membranes, leads to an emerging antibiotic crisis across the globe. To breathe life into existing drugs, we herein report a hypoxia-responsive nanoparticle (NP) that encapsulates a hydrophobic antibiotic, rifampicin, and a cationic potentiator, polysulfonium. The simultaneous release of antibiotics and potentiators can be promoted and inhibited in response to the severity of bacterial-induced hypoxia, leading to antimicrobial dosing in a precision manner. Under the synergism of polysulfoniums with membrane-disruption capability, the NPs can intensively decrease the antibiotic dose by up to 66–95% in eliminating planktonic Gram-negative P. aeruginosa bacteria and achieve an 8-log reduction of bacteria in mature biofilms at rifampicin MIC. The NP formulation demonstrates that precision dosing of antibiotics and potentiators regulated by hypoxia provides a promising strategy to maximize efficacy and minimize toxicity in treating Gram-negative bacterial infection.

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来源期刊
CiteScore
10.40
自引率
3.40%
发文量
209
审稿时长
1 months
期刊介绍: ACS Macro Letters publishes research in all areas of contemporary soft matter science in which macromolecules play a key role, including nanotechnology, self-assembly, supramolecular chemistry, biomaterials, energy generation and storage, and renewable/sustainable materials. Submissions to ACS Macro Letters should justify clearly the rapid disclosure of the key elements of the study. The scope of the journal includes high-impact research of broad interest in all areas of polymer science and engineering, including cross-disciplinary research that interfaces with polymer science. With the launch of ACS Macro Letters, all Communications that were formerly published in Macromolecules and Biomacromolecules will be published as Letters in ACS Macro Letters.
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