Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells.
Optimal gene therapy for tumors must deliver DNA to tumor cells with high efficiency and minimal toxicity. It has been reported that in non-viral gene delivery, the hydroxyethyl group at the amino terminal in cationic lipid was important for high transfection efficiency. Therefore, in this study, we developed new cationic nanoparticles (NP-OH) composed of cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine and Tween 80, and optimized in vitro and in vivo transfections for potential use as a non-viral DNA vector into human prostate tumor PC-3 cells and xenografts. In vitro transfection resulted in efficient DNA transfer when positive-charged nanoplex was prepared in the presence of sodium chloride (NaCl). In in vivo transfection, negative-charged nanoplex formed in water strongly induced the gene expression compared with positive-charged nanoplex when directly transfected into xenografts. These transfection efficiencies in vitro and in vivo were comparable to each commercial product. Furthermore, NP-OH nanoplexes displayed no induction of tumor necrosis factor (TNF)-alpha when administered by intravenous injection. The results of the experiments provided optimal conditions to form NP-OH nanoplex for gene delivery in vitro and in vivo. NP-OH is a potential non-viral DNA vector for the local treatment of tumor and in vitro.
Hattori
Yoshiyuki
Y
Department of Fine Drug Targeting Research, Institute of Medicinal Chemistry, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan. yhattori@hoshi.ac.jp <yhattori@hoshi.ac.jp>
Ding
Wu-xiao
WX
Maitani
Yoshie
Y
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D011136:Polysorbates / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012965:Sodium Chloride / Q000737:chemistry; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D011136:Polysorbates; D014409:Tumor Necrosis Factor-alpha; C106621:cholesteryl-3-carboxyamidoethylene-N-hydroxyethylamine; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D012965:Sodium Chloride; D004247:DNA; D002784:Cholesterol; D008156:Luciferases