title: Cholesterol-peptide hybrids to form liposome-like vesicles for gene delivery.
abstract: In this paper, four amphiphilic cholesterol-peptide conjugates (Ch-R5H5, Ch-R3H3, Ch-R5 and Ch-R5) were designed and synthesized, and their properties in gene delivery were evaluated in vitro with an aim of developing more efficient gene delivery carriers. These amphiphilic cholesterol-peptide conjugates are composed of hydrophobic cholesterol and positively charged peptides. They were able to self-assemble into micelles at low concentrations and their critical micelle concentrations in phosphate buffered saline (pH 7.4) are ≤85 µg/mL. Amphiphilic cholesterol-peptide conjugates condensed DNA more efficiently than a hydrophilic cationic oligoarginine (R10) peptide with no hydrophobic segment. Their transfection efficiencies were at least two orders of magnitude greater than that of R10 peptide in HEK-293 cells. Moreover, the introduction of histidine residues in cholesterol-peptide conjugates led to higher gene expression efficiency compared with cholesterol-peptides without histidine (Ch-R5 and Ch-R3), and the luciferase expression level was comparable or even higher than that induced by PEI at its optimal N/P ratio. In particular, Ch-R5H5 condensed DNA into smaller nanoparticles than Ch-R3H3 at higher N/P ratios, and the minimum size of Ch-R5H5/DNA complexes was 180 nm with zeta potential of 23 mV, achieved at the N/P ratio of 30. This liposome-like vesicle may be a promising gene delivery carrier for intravenous therapy.
authors: Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio, USA.
authors: Qiong
authors: Q
authors: Tang
authors: Bin
authors: B
authors: Cao
authors: Haiyan
authors: H
authors: Wu
authors: Gang
authors: G
authors: Cheng
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D046911:Macromolecular Substances / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D008823:Micelles; D010316:Particle Size; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature
chemical_list: D008081:Liposomes; D046911:Macromolecular Substances; D008823:Micelles; D010455:Peptides; D004247:DNA; D002784:Cholesterol
references: AAPS J. 2007 Feb 09;9(1):E18-29
references: 17408236
references: Adv Mater. 2009 Feb 23;21(8):847-867
references: 28413262
references: Biotechnol Adv. 2009 Jul-Aug;27(4):432-8
references: 19341789
references: Nature. 1997 Sep 18;389(6648):239-42
references: 9305836
references: Bioconjug Chem. 2003 Sep-Oct;14(5):979-88
references: 13129402
references: Br J Pharmacol. 2009 May;157(2):166-78
references: 19459843
references: Biotechnol J. 2009 Nov;4(11):1559-72
references: 19844918
references: Langmuir. 2012 Nov 20;28(46):16126-32
references: 23088373
references: Adv Drug Deliv Rev. 2001 Dec 3;53(1):75-94
references: 11733118
references: Curr Opin Struct Biol. 1996 Jun;6(3):334-41
references: 8804837
references: Nucleic Acids Res. 2005 May 24;33(9):e86
references: 15914665
references: J Control Release. 2010 Mar 3;142(2):267-76
references: 19861141
references: Nucleic Acids Res. 2002 Mar 15;30(6):1338-45
references: 11884631
references: Gene Ther. 2002 Dec;9(24):1647-52
references: 12457277
references: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references: 6606682
references: J Org Chem. 2008 Jun 20;73(12):4476-83
references: 18489153
references: Biochim Biophys Acta. 2005 Aug 1;1714(1):11-24
references: 16005847
references: Biomaterials. 2008 Dec;29(36):4838-46
references: 18829102
references: Nat Biotechnol. 2000 Jan;18(1):33-7
references: 10625387
references: Lancet. 1998 Jan 31;351(9099):346
references: 9652627
references: Curr Opin Biotechnol. 2002 Apr;13(2):128-31
references: 11950563
references: Nucleic Acids Res. 2003 Jun 1;31(11):2717-24
references: 12771197
references: Chem Rev. 2009 Feb;109(2):259-302
references: 19053809
references: Org Biomol Chem. 2003 Jul 21;1(14):2430-8
references: 12956058
references: Acc Chem Res. 2012 Jul 17;45(7):980-4
references: 22311735