title: Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.
abstract: The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.14). Compared to ordinary cationic liposomes (CLs), steric cationic liposomes (PEG-CLs) and 1% GA-PEG-CLs made from DOTAP/Chol/MPEG2000-Chol/GA-PEG-Chol at molar ratio of 50:45:4:1, 5% GA-PEG-CLs were found to possess the highest transfection efficiency as gene vectors in serum-free or serum-containing medium in PKCalpha over-expressed HepG2 cells but no significance difference in human embryonic kidney cell line HEK 293. Additionally, 5% GA-PEG-CLs have the lowest cytotoxicity on human normal hepatocyte cell line L02. The competitive inhibition experiments mediated by GA were carried out in HepG2 cells, which demonstrated that GA-PEG-CLs could deliver selectively pDNA to hepatoma cells by the targeting moiety GA. In conclusion, GA-PEG-CLs containing 5% GA-PEG-Chol might be one of the most potential gene vectors as hepatoma targeting therapy.
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Zhi Yao
authors.initials: ZY
authors.lastname: He
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Xiao Hua
authors.initials: XH
authors.lastname: Wu
authors.forename: Xiang Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Wen Fang
authors.initials: WF
authors.lastname: Wu
authors.forename: Shui
authors.initials: S
authors.lastname: Yu
authors.forename: Sheng Jun
authors.initials: SJ
authors.lastname: Mao
authors.forename: Yu Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000628:therapy; D002412:Cations; D002784:Cholesterol / Q000031:analogs & derivatives*; D005229:Fatty Acids, Monounsaturated; D015316:Genetic Therapy; D005822:Genetic Vectors; D006034:Glycyrrhetinic Acid; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000628:therapy; D010316:Particle Size; D011092:Polyethylene Glycols; D000644:Quaternary Ammonium Compounds; D014162:Transfection
chemical_list: D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C095164:poly(oxyethylene) cholesteryl ether; D011092:Polyethylene Glycols; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D006034:Glycyrrhetinic Acid