{"title":"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","authors":"Weiguang Bai, Yongjin Hu, Jinghua Zhao, Liuqi Shi, Chunhua Ge, Zhiyuan Zhu and Jingyi Rao*, ","doi":"10.1021/acsmacrolett.3c00365","DOIUrl":null,"url":null,"abstract":"<p >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 <i>P. aeruginosa</i> 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.</p>","PeriodicalId":18,"journal":{"name":"ACS Macro Letters","volume":"12 9","pages":"1193–1200"},"PeriodicalIF":5.2000,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria\",\"authors\":\"Weiguang Bai, Yongjin Hu, Jinghua Zhao, Liuqi Shi, Chunhua Ge, Zhiyuan Zhu and Jingyi Rao*, \",\"doi\":\"10.1021/acsmacrolett.3c00365\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >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 <i>P. aeruginosa</i> 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.</p>\",\"PeriodicalId\":18,\"journal\":{\"name\":\"ACS Macro Letters\",\"volume\":\"12 9\",\"pages\":\"1193–1200\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2023-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Macro Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsmacrolett.3c00365\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"POLYMER SCIENCE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Macro Letters","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsmacrolett.3c00365","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"POLYMER SCIENCE","Score":null,"Total":0}
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.
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.