题名 | Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance |
作者 | |
发表日期 | 2024-07-18 |
发表期刊 | Advanced Materials 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article ; Early Access |
关键词 | antibiotic resistance bacterial biofilms Imine bond formation murine pneumonia subcutaneous infections |
其他关键词 | COLISTIN |
摘要 | Polymyxins have been regarded as an efficient therapeutic against many life-threatening, multidrug resistant Gram-negative bacterial infections; however, the cytotoxicity and emergence of drug resistance associated with polymyxins have greatly hindered their clinical potential. Herein, the reaction-induced self-assembly (RISA) of polymyxins and natural aldehydes in aqueous solution is presented. The resulting assemblies effectively mask the positively charged nature of polymyxins, reducing their cytotoxicity. Moreover, the representative PMBA4 (composed of polymyxin B (PMB) and (E)-2-heptenal (A4)) assemblies demonstrate enhanced binding to Gram-negative bacterial outer membranes and exhibit multiple antimicrobial mechanisms, including increased membrane permeability, elevated bacterial metabolism, suppression of quorum sensing, reduced ATP synthesis, and potential reduction of bacterial drug resistance. Remarkably, PMBA4 assemblies reverse drug resistance in clinically isolated drug-resistant strains of Gram-negative bacteria, demonstrating exceptional efficacy in preventing and eradicating bacterial biofilms. PMBA4 assemblies efficiently eradicate Gram-negative bacterial biofilm infections in vivo and alleviate inflammatory response. This RISA strategy offers a practical and clinically applicable approach to minimize side effects, reverse drug resistance, and prevent the emergence of resistance associated with free polymyxins. The first example of reaction-induced self-assembly (RISA) is presented in the aqueous solution of antibiotics and adjuvants via dynamic covalent bonding. The resulting assemblies via RISA effectively mask the positive charge of polymyxins, preventing their interaction with negatively charged mammalian cells and reducing potential cytotoxicity, enhancing the bactericidal efficacy of polymyxins and preventing the emergence of further resistance. image |
资助项目 | National Key RD Program [2023YFB3809902]; National Natural Science Foundation of China [52293383, 22275043, 52203184, 52303181, 32102689]; Chinese National Foreign Experts Program for Belt and Road Initiative Innovative Talent Exchange [DL2022016004L]; Zhejiang Provincial Natural Science Foundation Outstanding Youth Project [LR24H180001]; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province [2022E10022]; Wenzhou Municipal Science and Technology Major Project [ZY2023031]; Startup Fund of Wenzhou Institute, University of Chinese Academy of Sciences [WIUCASQD2021022, WIUCASQD2021019]; Wenzhou Key Laboratory of Biomaterials and Engineering [WIUCASSWCL21006]; The 1000-Talent Program in Sichuan Province [2287, 1923]; Science and Technology Project of Sichuan Province [2022YFH0057]; Scientific Research Center of Wenzhou Medical University; Science and Technology Project of Sichuan Province [2022YFH0062, 2022ZYD0068]; Shanghai OE Biotech Co., Ltd. |
出版者 | WILEY-V C H VERLAG GMBH |
ISSN | 0935-9648 |
EISSN | 1521-4095 |
卷号 | 36期号:36 |
DOI | 10.1002/adma.202406156 |
页数 | 15 |
WOS类目 | Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter |
WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
WOS记录号 | WOS:001270529700001 |
收录类别 | SCIE ; EI ; SCOPUS ; PUBMED |
EI入藏号 | 20242916723055 |
EI主题词 | Self assembly |
EI分类号 | 461.9 Biology ; 462.5 Biomaterials (including synthetics) ; 951 Materials Science |
URL | 查看原文 |
PubMed ID | 39022883 |
SCOPUSEID | 2-s2.0-85198755604 |
通讯作者地址 | [Piao, Yinzi;Li, Yuanfeng;Liu, Yong]Wenzhou Med Univ, Joint Ctr Translat Med, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China. ; [Piao, Yinzi;Liu, Yong]Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325001, Zhejiang, Peoples R China. ; [Zhao, Xinghong]Sichuan Agr Univ, Ctr Sustainable Antimicrobials, Dept Pharm, Chengdu 611130, Peoples R China. ; [Liu, Yong]Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China. |
Scopus学科分类 | Materials Science (all);Mechanics of Materials;Mechanical Engineering |
SCOPUS_ID | SCOPUS_ID:85198755604 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/216692 |
专题 | 附属第一医院 口腔医学院、附属口腔医院 口腔医学院、附属口腔医院_正畸科 |
通讯作者 | Piao, Yinzi; Zhao, Xinghong; Li, Yuanfeng; Liu, Yong |
作者单位 | 1.Wenzhou Med Univ, Joint Ctr Translat Med, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Sch & Hosp Stomatol, Dept Orthodont, Wenzhou 325027, Zhejiang, Peoples R China; 3.Univ Chinese Acad Sci, Wenzhou Inst, Wenzhou 325001, Zhejiang, Peoples R China; 4.Sichuan Agr Univ, Ctr Sustainable Antimicrobials, Dept Pharm, Chengdu 611130, Peoples R China; 5.Wenzhou Med Univ, Dept Clin Lab, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China; 6.Iran Univ Med Sci, Cellular & Mol Res Ctr, Tehran 1449614535, Iran; 7.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China |
第一作者单位 | 附属第一医院; 口腔医学院、附属口腔医院; 正畸科 |
通讯作者单位 | 附属第一医院 |
第一作者的第一单位 | 附属第一医院 |
推荐引用方式 GB/T 7714 | Hu, Xiaowen,Li, Dongdong,Li, Huaping,et al. Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance[J]. Advanced Materials,2024,36(36). |
APA | Hu, Xiaowen., Li, Dongdong., Li, Huaping., Piao, Yinzi., Wan, Hongping., ... & Liu, Yong. (2024). Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance. Advanced Materials, 36(36). |
MLA | Hu, Xiaowen,et al."Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance".Advanced Materials 36.36(2024). |
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