Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes

被引:1
|
作者
Liu, Hang [1 ]
Wang, Lin [1 ]
Yao, Chen [1 ]
机构
[1] Southeast Univ, Sch Chem & Chem Engn, Nanjing 211189, Peoples R China
基金
中国国家自然科学基金;
关键词
antimicrobial peptide; beta-cyclodextrin; inclusion complexes; antibacterial activity; biosafety; ANTIMICROBIAL PEPTIDES; IN-VITRO; CYCLODEXTRINS; LENGTH; MODE; GOLD; ACID;
D O I
10.3390/ijms241914801
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)-modified tripeptide RWR (LA-RWR) with beta-cyclodextrin (beta-CD) to form nano-inclusion complexes. The free cationic tripeptide region in the nano-inclusion complex provided high antibacterial activity, while beta-CD enhanced its biocompatibility. Compared with peptides (LA-RWR, LA-RWR-phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram-negative/Gram-positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano-inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non-included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications.
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页数:18
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