- 作者： Chien-Hsin Lee Michael Hsiao Yun-Long Tseng Fu-Hsiung Chang
- 作者服務機構： Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- 中文摘要： --
- 英文摘要： Cationic liposome-mediated gene delivery to tumors hasmet with only limited success due to the low transfectionefficiency and lack of target specificity. We developed agene delivery system for HER-2-overexpressing cells byadding modified anti-HER-2 Fab' fragments to liposome/DNA complexes (lipoplexes). The modified anti-HER-2-Fab' was conjugated to liposomes containing cationiclipids such as 1,2-dioleoyl-3-(trimethylammonium) pro-pane and cholesterol (1:1 w/w) using a maleimido-poly-ethyleneglycol-3400-1, 2-dioleoyl-3-sn-phosphatidyle-thanolamine linker. The specific modification constrictedthe sizes of these immunolipoplexes to a range of 0.3-0.7μm, and they remained stable for a longer duration oftime compared to the lipoplex controls (0.8-3.2μm at4h). In addition, a 10-fold increase in luciferase activitywas achieved after transfecting human breast cancer SK-BR3 cells with immunolipoplexes as compared to thecontrol lipoplexes. Flow cytometry analysis demon-strated that 80％ of SK-BR3 cells expressed the green flu-orescent protein (GFP) 48 h after being transfected withimmunolipoplexes, while only 40％ of those with controllipoplexes and 3％ of those with naked DNA aloneexpressed GFP. Furthermore, the anti-HER-2 immunoli-poplexes showed specific enhancement of transfectionefficiency in HER-2-overexpressing SK-BR3 cells (a 6-foldincrease in luciferase activity) but not in HER-2-negativeMCF-7 breast cancer cells. The enhancement of genedelivery by anti-HER-2 immunoliposomes was not af-fected by the presence of serum. These results demon-strate the feasibility of improving target-specific genedelivery to HER-2-overexpressing cells by insertion oflipid-modified anti-HER-2-Fab' into the preformed lipo-somes.
- 中文關鍵字： --
- 英文關鍵字： HER-2 antibody. Immunolipoplex. Targeted gene delivery. Breast Cancer
