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Expression of squamous cell carcinoma antigen‐1 in liver enhances the uptake of hepatitis B virus envelope‐derived bio‐nanocapsules in transgenic rats
Author(s) -
Kasuya Takeshi,
Nomura Shintaro,
Matsuzaki Takashi,
Jung Joohee,
Yamada Tadanori,
Tatematsu Kenji,
Okajima Toshihide,
Tanizawa Katsuyuki,
Kuroda Shun’ichi
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06698.x
Subject(s) - hepatitis b virus , virus , liver cancer , hepatocellular carcinoma , in vivo , virology , biology , nanocapsules , tropism , apoptosis , cancer research , biochemistry , materials science , microbiology and biotechnology , nanoparticle , nanotechnology
We previously developed the bio‐nanocapsule, which consists of hepatitis B virus envelope L proteins. The bio‐nanocapsule can be used to deliver genes and drugs specifically to the human liver‐derived tissues in xenograft models, presumably by utilizing the human liver‐specific mechanism of hepatitis B virus infection. The hepatitis B virus tropism is highly restricted to humans and higher primates. Thus, to evaluate the in vivo therapeutic effects of forthcoming bio‐nanocapsule‐based medicines, it will be crucial to develop an animal model whose liver is susceptible to both bio‐nanocapsule and hepatitis B virus. In the present study, we aimed to establish a bio‐nanocapsule‐susceptible animal model using transgenic rats expressing squamous cell carcinoma antigen‐1 (SCCA1), which has been proposed to be a receptor for hepatitis B virus, interacting with the hepatitis B virus envelope protein and enhancing the cellular uptake of hepatitis B virus. We show that the recombinant SCCA1 protein interacts directly with bio‐nanocapsule and inhibits its attachment to the cultured human liver‐derived cells. Furthermore, we have established a transgenic rat that specifically expresses SCCA1 in the liver and also demonstrate that the amount of bio‐nanocapsule accumulated in the liver is significantly increased by the SCCA1 expression. Histological analysis suggests that bio‐nanocapsule is preferentially incorporated into the SCCA1‐expressing hepatocytes but not into macrophages, such as Küppfer cells, nor into endothelial cells. Therefore, this animal model is expected to be useful for the development of bio‐nanocapsule‐based medicines.