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Gene therapy of liver tumors with human liver-specific nanoparticles

Cancer Gene Therapy volume 14, pages 74–81 (2007)Cite this article

A Corrigendum to this article was published on 14 March 2007

Abstract

The development of safe and efficient liver-specific gene delivery approaches offers new perspectives for the treatment of liver disease, in particular, liver cancer. We evaluated the therapeutic potential of hepatotropic nanoparticles for gene therapy of liver tumor. These nanoparticles do not contain a viral genome and display the hepatitis B virus L antigen, which is essential to confer hepatic specificity. It has not been shown whether a therapeutic effect could be obtained using L nanoparticles in a human liver tumor xenograft model. Rats bearing human hepatic (NuE) and non-hepatic tumors were injected with L nanoparticles containing a green fluorescent protein (GFP) expression plasmid. GFP expression was observed only in NuE-derived tumors but not in the non-hepatic tumor. The potential for treatment of liver tumors was analyzed using L nanoparticles containing the herpes simplex virus thymidine kinase gene, in conjunction with ganciclovir pro-drug administration. The growth of NuE-derived tumors in L particle-injected rats was significantly suppressed, but not of the non-hepatic tumor control. In summary, this is the first demonstration that nanoparticles could be used for delivery of therapeutic genes with anti-tumor activity into human liver tumors. This intravenous delivery system may be one of the major advantages as compared to many other viral vector systems.

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Acknowledgements

We thank Takuji Tadakuma (the Department of Parasitology, National Defense Medical College) for the gift of the NuE cell line, and the HBV nanobioparticle team for technical support. This study was supported by the Grants-in-Aid from Ministry of Education, Culture, Sports, Science and Technology, Japan (the 21st century Center of Excellence program and Scientific Research). Thierry VandenDriessche and Marinee KL Chuah are supported by an FWO grant (G.0341.05) and a grant from the Flemish Government (VIB Dotation).

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Authors and Affiliations

  1. Department of Surgery, School of Medicine, Keio University, Tokyo, Japan

    Y Iwasaki, M Ueda & M Kitajima

  2. Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan

    T Yamada, K Tanizawa & S Kuroda

  3. Faculty of Engineering, Kobe University, Kobe, Hyogo, Japan

    A Kondo

  4. Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan

    M Seno

  5. Department of Pathology, School of Medicine, Keio University, Tokyo, Japan

    M Sakamoto

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  1. Y Iwasaki
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Correspondence to M Ueda.

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Iwasaki, Y., Ueda, M., Yamada, T. et al. Gene therapy of liver tumors with human liver-specific nanoparticles. Cancer Gene Ther 14, 74–81 (2007). https://doi.org/10.1038/sj.cgt.7700990

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