RRC ID 37596
Author Tabata A, Ohkubo Y, Anyoji N, Hojo K, Tomoyasu T, Tatematsu Y, Ohkura K, Nagamune H.
Title Development of a Sortase A-mediated Peptide-labeled Liposome Applicable to Drug-delivery Systems.
Journal Anticancer Res
Abstract BACKGROUND/AIM:In order to develop an efficient drug-delivery system (DDS), a lipopeptide-loaded liposome that functions as a platform for the transpeptidase reaction mediated by sortase A (SrtA) was constructed and its stability, as well as cell-specific targeting were evaluated in the present study.
MATERIALS AND METHODS:Several lipopeptides possessing an acceptor peptide sequence (oligoglycine ≥ three residues) or donor peptide sequence (LPETG) for the SrtA-mediated reaction were chemically synthesized and then inserted into the liposome membrane composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (DPPC-Chol-lipo) to obtain the lipopeptide-loaded liposomes. The transpeptidase reaction mediated by recombinant SrtA (His-ΔN59SrtA) was employed to modify the peptide moiety on the liposomal surface using a fluorescently-labeled substrate peptide corresponding to the species of each loaded lipopeptide. Furthermore, lung tumor-binding peptide (LTBP)-labeled liposomes, prepared by this transpeptidase reaction, were investigated for selective targeting to lung cancer cells in vitro.
RESULTS AND DISCUSSION:The His-ΔN59SrtA-mediated transpeptidation of fluorescently-labeled peptide on the lipopeptide-loaded DPPC-Chol-lipo was confirmed. The selective targeting of LTBP-labeled liposomes to the lung cancer cell line A549 was also observed in vitro. These results suggest that the labeling of acceptor or donor lipopeptide-loaded liposomes with the transpeptidase SrtA could be a useful method for developing a platform applicable to a cancer-targeting DDS.
Volume 35(8)
Pages 4411-7
Published 2015-8-1
PII 35/8/4411
PMID 26168480
MeSH 1,2-Dipalmitoylphosphatidylcholine / analogs & derivatives 1,2-Dipalmitoylphosphatidylcholine / chemistry Aminoacyltransferases / chemistry* Antineoplastic Agents / administration & dosage* Bacterial Proteins / chemistry* Cell Line, Tumor Cholesterol / chemistry Cholesterol / metabolism Cysteine Endopeptidases / chemistry* Drug Delivery Systems* Humans Lipopeptides / chemical synthesis Lipopeptides / chemistry* Liposomes / chemistry* Lung Neoplasms / drug therapy*
IF 1.994
Times Cited 8
WOS Category ONCOLOGY
Resource
Human and Animal Cells A549(RCB0098) NB1RGB(RCB0222)