TY - JOUR
T1 - A reduction-triggered delivery by a liposomal carrier possessing membrane-permeable ligands and a detachable coating
AU - Maeda, Takuro
AU - Fujimoto, Keiji
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (No. 14380412) from the Japan Society for the Promotion of Science and by a grant from Sekisui Co., Ltd.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/4/15
Y1 - 2006/4/15
N2 - To control the cellular uptake of drugs and genes, we synthesized a liposomal carrier possessing membrane-permeable ligands and a detachable poly(ethylene glycol) (PEG) coating. For the detachable coating, a lipid having a thiolytic cleavable spacer (PEG-S-S-DOPE) was synthesized by the reaction of dioleoylphosphatidylethanolamine (DOPE) with a PEG chain via a disulfide linkage. The liposomes were prepared from a mixture of dipalmitoylphosphatidylcholine (DPPC), DOPE, PEG-S-S-DOPE, and cholesteryl hemisuccinate (CHEMS). The octamer (R8 peptide) of arginine was chosen as the membrane-permeable ligand and covalently immobilized onto the CHEMS portion of the liposome surface (PEG-S-S-R8-liposome). The disulfide bond of the PEG chain was cleaved to display the R8 peptides on the liposome surface by adding a reducing agent such as l-cysteine, and thereby internalization of the liposomes was significantly facilitated. When l-cysteine was added to the mixture of cells and the liposome that incorporated plasmids encoding the enhanced green fluorescence protein (pEGFP), the expression of EGFP was low but could be observed in almost 100% of the cells.
AB - To control the cellular uptake of drugs and genes, we synthesized a liposomal carrier possessing membrane-permeable ligands and a detachable poly(ethylene glycol) (PEG) coating. For the detachable coating, a lipid having a thiolytic cleavable spacer (PEG-S-S-DOPE) was synthesized by the reaction of dioleoylphosphatidylethanolamine (DOPE) with a PEG chain via a disulfide linkage. The liposomes were prepared from a mixture of dipalmitoylphosphatidylcholine (DPPC), DOPE, PEG-S-S-DOPE, and cholesteryl hemisuccinate (CHEMS). The octamer (R8 peptide) of arginine was chosen as the membrane-permeable ligand and covalently immobilized onto the CHEMS portion of the liposome surface (PEG-S-S-R8-liposome). The disulfide bond of the PEG chain was cleaved to display the R8 peptides on the liposome surface by adding a reducing agent such as l-cysteine, and thereby internalization of the liposomes was significantly facilitated. When l-cysteine was added to the mixture of cells and the liposome that incorporated plasmids encoding the enhanced green fluorescence protein (pEGFP), the expression of EGFP was low but could be observed in almost 100% of the cells.
KW - Gene delivery
KW - Liposome
KW - Membrane-permeable
KW - PEG coating
KW - Reductive trigger
UR - http://www.scopus.com/inward/record.url?scp=33646086250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646086250&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2006.02.006
DO - 10.1016/j.colsurfb.2006.02.006
M3 - Article
C2 - 16574385
AN - SCOPUS:33646086250
SN - 0927-7765
VL - 49
SP - 15
EP - 21
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
IS - 1
ER -