Pegylated immuno-lipopolyplexes: A novel non-viral gene delivery system for liver cancer therapy.
In this study, pegylated immuno-lipopolyplexes (PILP), a novel and efficient gene delivery system was developed by employing DNA/polyethylenimine (PEI 25 kDa) polyplexes, as well as anionic liposomes composed of POPC, (DSPE)-PEG2000 and (DSPE)-PEG2000-biotin, at five different lipid/DNA molar ratios (50/1, 90/1, 130/1, 170/1 and 210/1), and by using streptavidin-monoclonal antibody conjugating through the biotin group located at the distal end of the PEG spacer as targeting antibody. This vector was highly effective in protecting DNA from enzyme digestion, and stable in particle size and zeta potential even after 20 day-storage at 4 degrees C. At the lipid/DNA molar ratio 170/1, the PILP were found to have the highest in vitro transfection efficiency with an average particle size of 132 nm and an average zeta potential of +9.5 mV. These complexes showed high efficiency in gene delivery to liver cancer cells with no significant cytotoxicity. Interestingly, the in vitro transfection efficiency did not decrease significantly up to 10 days of storage of PILP at 4 degrees C. Intravenous administration of the PILP resulted in tumor and liver targeted gene expression of the reporter genes EGFP and luciferase as opposed to the lung targeted gene expression obtained with PEI/DNA complexes, causing no cytokine production and liver injury. We conclude that the PILP are promising gene delivery systems which may be used to target the liver cancer.
Hu
Yurong
Y
School of Pharmacy, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.
Li
Kun
K
Wang
Lei
L
Yin
Shasha
S
Zhang
Zhenzhong
Z
Zhang
Yun
Y
D000818:Animals; D001710:Biotin / Q000235:genetics; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids / Q000235:genetics; D008081:Liposomes; D008099:Liver; D008113:Liver Neoplasms / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D011094:Polyethyleneimine / Q000008:administration & dosage; D014162:Transfection
D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D001710:Biotin; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases