Takeshi Kasuya

Osaka University, Ibaraki, Osaka-fu, Japan

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Publications (8)21.62 Total impact

  • Takeshi Kasuya, Shun'ichi Kuroda
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    ABSTRACT: A wide variety of nanoparticles (NPs) that can deliver incorporated therapeutic materials such as compounds, proteins, genes and siRNAs to the human liver have been developed to treat liver-related diseases. This review describes NP-based drug and gene delivery systems such as liposomes (including lipoplex), polymer micelles, polymers (including polyplex) and viral vectors. It focuses upon the modification of these NPs to enhance liver specificity or delivery efficiency in vitro and in vivo. We discuss recent advances in drug and gene delivery systems specific to the human liver utilizing bio-nanocapsules comprising hepatitis B virus (HBV) envelope L protein, which has a pivotal role in HBV infection. These NP-based medicines may offer novel strategies for the treatment of liver-related diseases and contribute to the development of nanomedicines targeting other tissues.
    Expert Opinion on Drug Delivery 02/2009; 6(1):39-52. · 4.87 Impact Factor
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    ABSTRACT: A bio-nanocapsule (BNC) is an ~50-nm hepatitis B virus (HBV) subviral particle comprising HBV envelope L proteins and a lipid bilayer, and is synthesized in recombinant Saccharomyces cerevisiae. When BNCs are administered intravenously in a mouse xenograft model, they can accumulate specifically in human liver-derived tissues and enter cells efficiently by the HBV-derived human liver-specific infection machinery, localized at the outer-membrane pre-S region of the L protein. BNC specificity for the human liver can be altered to other tissues by substituting the pre-S region using targeting molecules (e.g., antibodies, lectins, cytokines). BNCs can spontaneously form complexes with liposomes (LPs) by the membrane fusogenic activity of the pre-S region. LPs containing various therapeutic materials (e.g., chemicals, proteins, DNA, RNA) can therefore be covered with BNCs to form an ~150-nm BNC-LP conjugate. BNC-LP conjugates injected intravenously can deliver incorporated materials to target tissues specifically and efficiently by utilizing the HBV-derived infection machinery. The stability of BNC-LP conjugates in the blood circulation is similar to that of PEGylated LPs. In this chapter, we describe the preparation and in vivo application of BNC-LP conjugates, and the potential of BNC-LP conjugates as in vivo pinpoint drug delivery systems.
    Methods in enzymology 01/2009; 464:147-66. · 1.90 Impact Factor
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    ABSTRACT: A bio-nanocapsule (BNC) is an ~50-nm hepatitis B virus (HBV) subviral particle comprising HBV envelope L proteins and a lipid bilayer, and is synthesized in recombinant Saccharomyces cerevisiae. When BNCs are administered intravenously in a mouse xenograft model, they can accumulate specifically in human liver-derived tissues and enter cells efficiently by the HBV-derived human liver-specific infection machinery, localized at the outer-membrane pre-S region of the L protein. BNC specificity for the human liver can be altered to other tissues by substituting the pre-S region using targeting molecules (e.g., antibodies, lectins, cytokines). BNCs can spontaneously form complexes with liposomes (LPs) by the membrane fusogenic activity of the pre-S region. LPs containing various therapeutic materials (e.g., chemicals, proteins, DNA, RNA) can therefore be covered with BNCs to form an ~150-nm BNC–LP conjugate. BNC–LP conjugates injected intravenously can deliver incorporated materials to target tissues specifically and efficiently by utilizing the HBV-derived infection machinery. The stability of BNC–LP conjugates in the blood circulation is similar to that of PEGylated LPs. In this chapter, we describe the preparation and in vivo application of BNC–LP conjugates, and the potential of BNC–LP conjugates as in vivo pinpoint drug delivery systems.
    Methods in Enzymology - METH ENZYMOLOGY. 01/2009; 464:147-166.
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    ABSTRACT: 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.
    FEBS Journal 12/2008; 275(22):5714-24. · 4.25 Impact Factor
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    ABSTRACT: Metastasis is a key aspect of tumor malignancy, and several malignant tumors show expression of various mature N-type glycans. In particular, beta1-6 branching N-acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L(4) isolectin (L(4)-PHA), which adheres to beta1-6 GlcNAc specifically, has been used for in situ cancer diagnosis. Bionanocapsules (BNCs), hollow particles with a diameter of approximately 80 nm and composed of hepatitis B surface antigen (HBsAg) and a lipid bilayer, have been developed as human liver-specific nanocapsules for in vivo drug delivery system. In this study, we have generated L(4)-PHA-displaying BNCs (PHA-BNCs) and examined whether L(4)-PHA could retarget the BNCs to malignant tumors as a "biosensor" distinguishing tumor metastaticity. Fluorescence-labeled PHA-BNCs injected systemically into a mouse xenograft model were found to accumulate in beta1-6 GlcNAc-expressing malignant tumors. The PHA-BNCs were able to deliver DNA to the malignant cancer cells. These results open up the possibility of using L(4)-PHA lectin as a targeting molecule in a drug delivery system, and of using PHA-BNCs as a novel nanodevice for malignant tumor-specific bioimaging and drug delivery.
    Human gene therapy 09/2008; 19(9):887-95. · 4.20 Impact Factor
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    ABSTRACT: Human hepatocyte-specific delivery of green fluorescent protein was succeeded in the mouse xenograft model by fusion with hepatitis B virus surface antigen pre-S regions (pre-S(1+2)), not with each pre-S region. The entire pre-S region would be useful for human liver-specific delivery of therapeutic proteins and bio-imaging fluoroproteins in biomedical field.
    Journal of Bioscience and Bioengineering 08/2008; 106(1):99-102. · 1.74 Impact Factor
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    ABSTRACT: Metastasis is a key aspect of a tumorfs malignancy, and several malignant tumors show expression of various matured N-type glycans. In particular, beta1-6 branching N-acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L4 isolectin (L4-PHA), which adheres to beta1-6GlcNAc specifically, has been used for in situ cancer diagnosis. Bio-nanocapsule (BNC) is an approximately 80-nm hollow particle composed of hepatitis B surface antigen (HBsAg) and lipid bilayer, and has been developed as a human liver-specific nanocapsule for in vivo drug delivery system (DDS). In this study, we have generated an L4-PHA-displaying BNC (PHA-BNC), and examined whether L4-PHA could retarget BNC to the malignant tumors as a ebio-sensorf distinguishing tumor metastaticity. Fluorescence-labeled PHA-BNC systemically injected to a mouse xenograft model was found to accumulate in the beta1-6GlcNAc-expressing malignant tumor. The PHA-BNC could deliver DNA to the malignant cancer cells. These results open up the possibility of L4-PHA lectin as a targeting molecule for DDS, and PHA-BNC as a novel nanodevice for the malignant tumor-specific bio-imaging and DDS.
    Human gene therapy 07/2008; · 4.20 Impact Factor
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    ABSTRACT: To maximize the beneficial effects and minimize the side effect of drugs, DDS (drug delivery system) has been attracted many researchers in the recent drug development. Especially, the in vivo pinpoint delivery system for drugs is very important and key technology for developing the next generations of anti-cancer drugs and gene therapies. Bio-nanocapsule (BNC) is recombinant yeast-derived hepatitis B virus surface antigen particle, which has been used as a recombinant hepatitis B vaccine for the last 20 years in the world. BNC can incorporate various materials (chemical compounds, proteins, genes, siRNA, etc) by the fusion with liposome, and deliver them to the organs and tissues in vivo specifically by the action of bio-recognition molecules on the BNC's surface. The transfection efficiency is significantly higher than that of liposome, because BNC harbors the complete set of hepatitis B virus infection machinery. Recently, we succeeded in the in vivo retargeting of BNC by displaying either antibody or homing peptide, less than 10 amino acid residues for in vivo targeting. BNC is a hybrid of liposome and virus, and very flexible system for in vivo retargeting. BNC might be very promising carriers in the next generation of DDS.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 06/2007; 127(5):797-805. · 0.46 Impact Factor