Document Detail

Cytoplasmic delivery of liposomal contents mediated by an acid-labile cholesterol-vinyl ether-PEG conjugate.
MedLine Citation:
PMID:  19072698     Owner:  NLM     Status:  MEDLINE    
An acid-cleavable PEG lipid, 1'-(4'-cholesteryloxy-3'-butenyl)-omega-methoxy-polyethylene[112] glycolate (CVEP), has been developed that produces stable liposomes when dispersed as a minor component (0.5-5 mol %) in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Cleavage of CVEP at mildly acidic pHs results in dePEGylation of the latently fusogenic DOPE liposomes, thereby triggering the onset of content release. This paper describes the synthesis of CVEP via a six-step sequence starting from the readily available precursors 1,4-butanediol, cholesterol, and mPEG acid. The hydrolysis rates and release kinetics from CVEP/DOPE liposome dispersions as a function of CVEP loading, as well as the cryogenic transmission electron microscopy and pH-dependent monolayer properties of 9:91 CVEP/DOPE mixtures, also are reported. When folate receptor-positive KB cells were exposed to calcein-loaded 5:95 CVEP/DOPE liposomes containing 0.1 mol % folate-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene[76] glycolamide (folate-PEG-DSPE), delivery of the calcein cargo to the cytoplasm of the cells was observed as determined by fluorescence microscopy and flow cytometry. Fluorescence resonance energy transfer analysis of lipid mixing in these cells was consistent with membrane-membrane fusion between the liposome and endosomal membranes.
Jeremy A Boomer; Marquita M Qualls; H Dorota Inerowicz; Robert H Haynes; V Srilakshmi Patri; Jong-Mok Kim; David H Thompson
Related Documents :
8821118 - Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: a common li...
10748048 - Disruption of the oxysterol 7alpha-hydroxylase gene in mice.
8857918 - Apob-100 secretion by hepg2 cells is regulated by the rate of triglyceride biosynthesis...
8170288 - Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synt...
16787318 - Investigation of bioisosteric effects on the interaction of substrates/ inhibitors with...
16833788 - Products and mechanisms of the reaction of oleic acid with ozone and nitrate radical.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  20     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-21     Completed Date:  2009-03-23     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  47-59     Citation Subset:  IM    
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-1393, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cytoplasm / metabolism*
Fluoresceins / administration & dosage*
Fluorescence Resonance Energy Transfer
Liposomes / pharmacokinetics*
Polyethylene Glycols*
Vinyl Compounds*
Grant Support
GM55266/GM/NIGMS NIH HHS; R01 GM055266-02/GM/NIGMS NIH HHS; R01 GM055266-03/GM/NIGMS NIH HHS; R01 GM055266-04/GM/NIGMS NIH HHS; R01 GM087016-04/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Fluoresceins; 0/Liposomes; 0/Polyethylene Glycols; 0/Vinyl Compounds; 2H2T044E11/vinyl ether; 57-88-5/Cholesterol; V0YM2B16TS/fluorexon

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Correlation of relaxivity with coordination number in six-, seven-, and eight-coordinate Mn(II) comp...
Next Document:  Olefinic-lactone cyclizations to macrocycles.