Gene therapy of liver tumors with human liver-specific nanoparticles

Y. Iwasaki, M. Ueda, T. Yamada, A. Kondo, M. Seno, K. Tanizawa, S. Kuroda, Michiie Sakamoto, M. Kitajima

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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.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalCancer Gene Therapy
Volume14
Issue number1
DOIs
Publication statusPublished - 2007 Jan 22

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Keywords

  • Gene therapy
  • HBsAg L nanoparticle
  • HSV-tk/GCV system
  • Liver tumor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Iwasaki, Y., Ueda, M., Yamada, T., Kondo, A., Seno, M., Tanizawa, K., Kuroda, S., Sakamoto, M., & Kitajima, M. (2007). Gene therapy of liver tumors with human liver-specific nanoparticles. Cancer Gene Therapy, 14(1), 74-81. https://doi.org/10.1038/sj.cgt.7700990