https://scholars.lib.ntu.edu.tw/handle/123456789/452199
標題: | Enhanced gene delivery to HER-2-overexpressing breast cancer cells by modified immunolipoplexes conjugated with the anti-HER-2 antibody | 作者: | Lee C.-H. Hsiao M. Tseng Y.-L. FU-HSIUNG CHANG |
關鍵字: | Breast cancer; HER-2 antibody; Immunolipoplex; Targeted gene delivery | 公開日期: | 2003 | 卷: | 10 | 期: | 3 | 起(迄)頁: | 337-344 | 來源出版物: | Journal of Biomedical Science | 摘要: | Cationic liposome-mediated gene delivery to tumors has met with only limited success due to the low transfection efficiency and lack of target specificity. We developed a gene delivery system for HER-2-overexpressing cells by adding modified anti-HER-2 Fab′ fragments to liposome/DNA complexes (lipoplexes). The modified anti-HER-2-Fab′ was conjugated to liposomes containing cationic lipids such as 1,2-dioleoyl-3-(trimethylammonium) propane and cholesterol (1:1 w/w) using a maleimido-polyethyleneglycol-3400-1,2-dioleoyl-3-sn-phosphatidylethanolamine linker. The specific modification constricted the sizes of these immunolipoplexes to a range of 0.3-0.7 μm, and they remained stable for a longer duration of time compared to the lipoplex controls (0.8-3.2 μm at 4 h). In addition, a 10-fold increase in luciferase activity was achieved after transfecting human breast cancer SK-BR3 cells with immunolipoplexes as compared to the control lipoplexes. Flow cytometry analysis demonstrated that 80% of SK-BR3 cells expressed the green fluorescent protein (GFP) 48 h after being transfected with immunolipoplexes, while only 40% of those with control lipoplexes and 3% of those with naked DNA alone expressed GFP. Furthermore, the anti-HER-2 immunolipoplexes showed specific enhancement of transfection efficiency in HER-2-overexpressing SK-BR3 cells (a 6-fold increase in luciferase activity) but not in HER-2-negative MCF-7 breast cancer cells. The enhancement of gene delivery by anti-HER-2 immunoliposomes was not affected by the presence of serum. These results demonstrate the feasibility of improving target-specific gene delivery to HER-2-overexpressing cells by insertion of lipid-modified anti-HER-2-Fab′ into the preformed liposomes. Copyright ? 2003 National Science Council, ROC and S. Karger AG, Basel. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0344080421&doi=10.1159%2f000070099&partnerID=40&md5=5a332d2000638c01709b0f7664d0c90c https://scholars.lib.ntu.edu.tw/handle/123456789/452199 |
ISSN: | 10217770 | DOI: | 10.1159/000070099 | SDG/關鍵字: | 1,2 dioleoyl 3 (trimethylammonium)propane; antibody conjugate; cation; cholesterol; dioleoylphosphatidylethanolamine; green fluorescent protein; immunoglobulin F(ab) fragment; immunoliposome; lipid; luciferase; maleimido polyethylene glycol 3400; protein antibody; unclassified drug; article; breast adenocarcinoma; cancer cell; complex formation; conjugation; controlled study; DNA modification; DNA transfection; drug efficacy; enzyme activity; flow cytometry; gene overexpression; gene targeting; human; human cell; lipid analysis; oncogene neu; priority journal; productivity; Antibodies, Neoplasm; Cell Line, Tumor; Flow Cytometry; Gene Targeting; Humans; Liposomes; Receptor, erbB-2; Transfection; Mink cell focus-forming virus |
顯示於: | 生物化學暨分子生物學科研究所 |
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