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Hepatoma-targeted gene delivery using a tumor cell-specific gene regulation system combined with a human liver cell-specific bionanocapsule

Jeong-Hun Kanga 1 , Jun Oishia b 2 , Jong-Hwan Kimc , Moeko Ijuina b , Riki Toitaa b , Byungdug Junc , Daisuke Asaid , Takeshi Moria b , Takuro Niidomea b f , Katsuyuki Tanizawae , Shun’ichi Kurodae , Yoshiki Katayamaa b f Corresponding Author Informationemail address

Received 4 July 2009; received in revised form 10 December 2009; accepted 15 January 2010. published online 05 February 2010.
Accepted Manuscript

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 C (PKC)α in hepatoma cells. The complex of the polymer/DNA with BNC 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 PKCα and BNC showed novel potential for the selective treatment of hepatomas. The system could be a useful method with applications in hepatoma-specific gene therapy and molecular imaging.

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a Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan

b Graduate School of Systems Life Sciences, Kyushu University, Motooka 729, Nishi-ku, Fukuoka 819-0395, Japan

c Faculty of Education, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

d Department of Microbiology St. Marianna University School of Medicine 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan

e Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan

f Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan

Corresponding Author InformationCorresponding author. Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan. Tel./fax: +81 92 802 2850.

1 These authors contributed equally to this work.

2 These authors contributed equally to this work.

PII: S1549-9634(10)00014-6

doi:10.1016/j.nano.2010.01.007

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