一步酸化法制备抗菌肽胶束及其抗菌性能研究  

Antibacterial Micelles Self-assembled from Copolypeptides through a One-step Acidification Process

作　　者：江金辉 杨雨嬴 凡刘杰 朱云卿 杜建忠 Jin-hui Jiang;Yu-ying Yang;Liu-jie Fan;Yun-qing Zhu;Jian-zhong Du(Department of Orthopedics,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072;Department of Polymeric Materials,School of Materials Science and Engineering,Tongji University,Shanghai 201804)

机构地区：[1]同济大学附属第十人民医院骨科,上海200072 [2]同济大学材料科学与工程学院高分子材料系,上海201804

出　　处：《高分子学报》2021年第12期1559-1567,I0002,共10页Acta Polymerica Sinica

基　　金：国家杰出青年科学基金(基金号21925505);国家自然科学基金(基金号51903190);上海市科委国际合作项目(项目号21520710100);上海市浦江人才计划(项目号19PJ1409600)资助项目.

摘　　要：提出了简化抗菌肽纳米粒子制备流程的“一步酸化法”.利用[1-(4-氨基苯基)-1,2,2-三苯基]乙烯(TPE-NH2)引发Nε-三氟乙酰基-L-赖氨酸环内酸酐[Lys(Tfa)NCA]和L-谷氨酸-γ-苄酯环内酸酐(BLG NCA)单体的开环共聚,然后选择性脱除三氟乙酰保护基,制备了无规共聚多肽TPE-P(Lys28-stat-BLG16).随后,采取一步酸化法直接制备了共聚多肽胶束溶液.抗菌实验结果表明,该抗菌肽胶束对大肠杆菌及金黄色葡萄球菌的最低抑菌浓度分别为256和64μg/mL,最低杀菌浓度分别为400和100μg/mL.此外,由于其四苯乙烯(TPE)端基具有聚集诱导发光效应,该抗菌肽胶束还有望用于可视化探究抗菌机理.We propose a one-step acidification method for facile preparation of antibacterial micelles.The random copolypeptide TPE-P(Lys28-stat-BLG16)was obtained by selective deprotection of the trifluoroacetyl groups from a TPE-P[Lys(Tfa)28-stat-BLG16]precursor.This initial random copolypeptide was synthesized by ring-opening copolymerization of Nε-trifluoroacetyl-L-lysine N-carboxyanhydride[Lys(Tfa)NCA]andγ-benzyl-L-glutamate N-carboxyanhydride(BLG NCA)using 4-(1,2,2-triphenylvinyl)aniline(TPE-NH2)as initiator.After polymerization and deprotection,polymer micelles were formed by acidification of the crude aqueous TPE-P(Lys28-stat-BLG16)reaction mixture.Thus,this method is called a"one-step acidification process".The obtained micelles should have good antibacterial properties,given that this random copolypeptide comprises a large number of aromatic and amino groups.The antibacterial properties of these micelles were evaluated using the broth microdilution method and the plate paint method,to determine the minimum inhibitory concentration(MIC)and the minimum bacteri‐cidal concentration(MBC).These tests showed that these polymer micelles have indeed antibacterial properties:the determined MICs for E.coli and S.aureus were 256 and 64μg/mL;the determined MBCs for these bacteria were 400 and 100μg/mL,respectively.Interestingly,these antibacterial micelles produce bright blue fluorescence light under UV exposure,owing to the aggregation-induced emission(AIE)effect of the TPE end groups.Herein,this property was used to optically explore the antibacterial mechanism of these polymer micelles.This approach indi-cated that these polymer micelles kill bacteria by piercing their membrane via a physically damaging process.

关 键 词：聚多肽 一步酸化法 胶束 自组装 抗菌 

分 类 号：TQ936.16[化学工程]