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Enhanced gene delivery to HER-2-overexpressing breast cancer cells by modified immunolipoplexes conjugated with the anti-HER-2 antibody

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

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-poly-ethyleneglycol-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.

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Authors and Affiliations

  1. Room 911, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sec. 1, 100, Taipei, Taiwan (ROC)

    Chien-Hsin Lee, Yun-Long Tseng &  Fu-Hsiung Chang

  2. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC

    Michael Hsiao

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  1. Chien-Hsin Lee
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  2. Michael Hsiao
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  4. Fu-Hsiung Chang
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Lee, CH., Hsiao, M., Tseng, YL. et al. Enhanced gene delivery to HER-2-overexpressing breast cancer cells by modified immunolipoplexes conjugated with the anti-HER-2 antibody. J Biomed Sci 10, 337–344 (2003). https://doi.org/10.1007/BF02256453

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  • DOI: https://doi.org/10.1007/BF02256453

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