Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.
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.
He
Zhi Yao
ZY
West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China.
Zheng
Xi
X
Wu
Xiao Hua
XH
Song
Xiang Rong
XR
He
Gu
G
Wu
Wen Fang
WF
Yu
Shui
S
Mao
Sheng Jun
SJ
Wei
Yu Quan
YQ
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
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