Hepatoma-targeted gene delivery using a tumor cell-specific gene regulation system combined with a human liver cell-specific bionanocapsule.
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 alpha 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 C alpha 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 editor: Hepatocellular 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.
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan.
Jeong-Hun
JH
Kang
Jun
J
Oishi
Jong-Hwan
JH
Kim
Moeko
M
Ijuin
Riki
R
Toita
Byungdug
B
Jun
Daisuke
D
Asai
Takeshi
T
Mori
Takuro
T
Niidome
Katsuyuki
K
Tanizawa
Shun'ichi
S
Kuroda
Yoshiki
Y
Katayama
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D014407:Tumor Cells, Cultured
D053769:Nanocapsules; D009842:Oligopeptides