title: A designed lipopeptide with a leucine zipper as an imbedded on/off switch for lipid bilayers.
abstract: Thermo-sensitive drug carriers are receiving increasing attention for use with localized hyperthermia at abnormal tissue sites or to easily implement hyperthermia. In this study, a thermo-sensitive lipopeptide was designed, consisting of a carbon chain and a leucine zipper with an amino acid sequence CH3-(CH2)4-CO-NH-VAQLEVK-VAQLESK-VSKLESK-VSSLESK-COOH. They could form dimers by the hydrophobic force at body temperature and separate into single random coils above the melting temperature (Tm). The lipopeptide was mixed with phospholipids to form a hybrid liposome (Lipo-LPe). The Tm of the free lipopeptide and lipopeptide in Lipo-LPe was found to be 48.0 °C and 42.5 °C from circular dichroism data, respectively. Compared with the pure liposome, the phase-transition temperature (Ttr) of Lipo-LPe, which was obtained by differential scanning calorimetry, was increased by about 5 °C, showing an improvement of thermal stability. The drug release rate of Lipo-LPe was slightly decreased at body temperature but greatly increased at mild hyperthermia in vitro. Drug release under intermittent heating was performed, and the reversibility of thermo-sensitive on/off switch was confirmed. Furthermore, Lipo-LPe achieved the maximum amount of cell death under mild hyperthermia. We concluded that Lipo-LPe, as a novel thermo-sensitive drug carrier, provides a promising opportunity for controlling drug release.
authors.affiliation: Key Laboratory for Advanced Materials and Department of Chemistry, East China University of Science and Technology, Shanghai, 200237, P. R. China. xushouhong@ecust.edu.cn hlliu@ecust.edu.cn.
authors.forename: Sijia
authors.initials: S
authors.lastname: Wang
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Shen
authors.forename: Junqi
authors.initials: J
authors.lastname: Zhang
authors.forename: Shouhong
authors.initials: S
authors.lastname: Xu
authors.forename: Honglai
authors.initials: H
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D005454:Fluorescence Polarization; D006801:Humans; D016350:Leucine Zippers; D008051:Lipid Bilayers; D055666:Lipopeptides / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission
chemical_list: D008051:Lipid Bilayers; D055666:Lipopeptides; D004317:Doxorubicin