文献类型：期刊文献

英文题名：Synthetic Mimics of Antimicrobial Peptides for the Targeted Therapy of Multidrug-Resistant Bacterial Infection

作者：Gong, Chenyu[1];Sun, Junjie[1];Xiao, Yan[1];Qu, Xue[1];Lang, Meidong[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Key Lab Ultrafine Mat, Minist Educ,Sch Mat Sci & Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：10

期号：22

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20213410794357);WOS:【SCI-EXPANDED(收录号:WOS:000686141000001)】；

基金：C.Y.G. and J.J.S. contributed equally to this work. Financial support from the National Natural Science Foundation of China (21674037 and 31922041), the Natural Science Foundation of Shanghai (18ZR1410200), the National Key Research and Development Program (2016YFC1100703) and the Science and Technology Commission of Shanghai Municipality (18JC1410802) are gratefully acknowledged.

语种：英文

外文关键词：antibacterial polypeptides; bacterial infection; multidrug-resistant bacteria; pH-responsive polypeptides

摘要：Antibacterial materials are highly demanded in treatment of bacterial infection, especially severe ones with multidrug-resistance. Herein, pH-responsive polypeptide, i.e., poly-L-lysine modified by 1-(propylthio)acetic acid-3-octylimidazolium and citraconic anhydride (PLL-POIM-CA), is synthesized by post-polymerization modification of poly-L-lysine (PLL) with 1-(propylthio)acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA). It is observed that PLL-POIM-CA is stable under normal physiological condition, while CA cleaves rapidly at weakly acidic environment like bacterial infectious sites. The hydrolyzed PLL-POIM-CA exhibits excellent broad-spectrum antibacterial activities against Gram-negative bacteria of Escherichia coli and Gram-positive bacteria of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). In particular, the minimum inhibitory concentration (MIC) against multidrug-resistant bacteria like MRSA is as low as 7.8 mu g mL(-1). Moreover, PLL-POIM-CA exhibits good biocompatibility with mouse fibroblast cells (L929) in vitro and improved hemocompatibility with an HC50 exceeding 5000 mu g mL(-1). Therefore, PLL-POIM-CA displays an excellent bacteria versus cells selectivity (HC50/MIC) over 534, which is 53 times higher than natural antimicrobial peptide of indolicidin. It is further demonstrated in vivo that the antimicrobial polypeptide effectively accelerates MRSA-infected wound healing by relieving local inflammatory response. Therefore, this targeted antimicrobial polypeptide has broad application prospects for the treatment of multidrug-resistant bacterial infection.