文献类型：期刊文献

英文题名：pH/Redox-Controlled Interaction between Lipid Membranes and Peptide Derivatives with a "Helmet"

作者：Li, Mengya[1];Wang, Sijia[2];Xu, Jun[1];Xu, Shouhong[1];Liu, Honglai[1]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]Henan Univ Chinese Med, Coll Pharm, Zhengzhou 450046, Henan, Peoples R China

年份：2019

卷号：123

期号：31

起止页码：6784

外文期刊名：JOURNAL OF PHYSICAL CHEMISTRY B

收录：;EI(收录号：20193507360753);WOS:【SCI-EXPANDED(收录号:WOS:000480502800014)】；

基金：Financial support for this work was provided by the National Natural Science Foundation of China (no. 21776071) and the National Natural Science Foundation of China for Innovative Research Groups (no. 51621002).

语种：英文

外文关键词：Supramolecular chemistry - Lipid bilayers - Lipids - Liposomes - Cells - Cytology

摘要：How to reduce the cytotoxicity of antitumor peptides to normal cells remains an ongoing challenge. Here, we designed a pH/redox-responsive supramolecular structure (Pep-V subset of P-PEG) composed of a peptide modified with viologen (Pep-V) and polyethylene glycol bearing pillar[5]arene (P-PEG) as a "helmet". By shielding the hydrophobic moiety of the peptide derivative with pillar[5]arene via host-guest interactions, its disruption on normal cells can be effectively reduced. At acidic pH, the supramolecular structure can selectively adsorb onto negatively charged lipid membranes because of electrostatic interactions. Owing to redox responsiveness of the viologen group, Pep-V could be separated from P-PEG after the addition of reductants and inserted into lipid bilayers, which leads to membrane disruption. Cargo leakage of liposome models was investigated to understand Pep-V subset of P-PEG-induced liposomal membrane disruption under different pH values and redox conditions. Results showed that Pep-V subset of P-PEG caused almost no cargo leakage from (1,2-dipalmitoyl-sn-glycerol-3-phosphocholine) liposomes at pH 7.4 but significant leakage from negatively charged (1,2-dipalmitoyl-sn-glycerol-3-phospho-(1-rac-glyerol)) liposomes at pH 5.0 under a reducing environment. Pep-V subset of P-PEG displayed low destructive effects on mimic normal cells and significant disruption to mimic tumor cells when exposed to a reducing environment that is expected to be a potential antitumor agent.