Hepatoma-targeted gene delivery using a tumor cell–specific gene regulation system combined with a human liver cell–specific bionanocapsule |
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Authors: | Jeong-Hun Kang Jun Oishi Jong-Hwan Kim Moeko Ijuin Riki Toita Byungdug Jun Daisuke Asai Takeshi Mori Takuro Niidome Katsuyuki Tanizawa Shun'ichi Kuroda Yoshiki Katayama |
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Affiliation: | 1. Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan;2. Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan;3. Faculty of Education, Nagasaki University, Nagasaki, Japan;4. Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Japan;5. Center for Future Chemistry, Kyushu University, Fukuoka, Japan;6. Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan |
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Abstract: | Hepatoma (hepatocellular carcinoma) is the most common type of malignant tumor originating in the liver and has a relatively low 5-year survival rate. The development of hepatoma-targeted therapy is needed to increase treatment efficiency and to reduce the incidence of undesirable side effects. In this study we developed a novel hepatoma-targeted gene delivery system. The gene delivery system was prepared by combining a human liver cell–specific bionanocapsule (BNC) and a tumor cell–specific gene regulation polymer, which responds to hyperactivated protein kinase Cα in hepatoma cells. The complex of the polymer-DNA with BNCs was delivered into cells and tissues. The developed system showed increased transfection efficiency and resulted in cell-specific gene expression in hepatoma cells and tissues (HuH-7), but no gene expression in normal human hepatocytes or human epidermoid tumor cells (A431). The combination of a tumor cell-specific gene regulation system responding to protein kinase Cα and BNCs showed excellent potential for the selective treatment of hepatomas. The system could be a useful method with applications in hepatoma-specific gene therapy and molecular imaging.From the Clinical EditorHepatocellular carcinoma is the most common type of malignant tumor in the liver with a low 5-year survival rate. In this study, a novel hepatoma-targeted gene delivery system was prepared by combining a human liver cell-specific bionanocapsule and a tumor cell-specific gene regulation polymer, which responds to hyperactivated protein kinase C (PKC)a in hepatoma cells. The system could be a useful in hepatoma-specific gene therapy and molecular imaging. |
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