title: Human liver-specific nanocarrier in a novel mouse xenograft model bearing noncancerous human liver tissue.
abstract: For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule. Interestingly, human liver tissues were engrafted in 58% of the animals at least for 14 days shown by a human hepatocyte-specific antibody. The engineered HBV nanoparticles which contained fluorescent chemicals could selectively bind to the xenograft in these immune-deficient mice when they were administered systemically. These results suggested that the model animal was usable to demonstrate the efficacy of the nanoparticles that could deliver chemicals specific to the normal human liver tissue by systemic administration, which will facilitate the study of human liver cell biology, drug metabolism and infections with hepatotropic viruses.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Koichi
authors.initials: K
authors.lastname: Aiura
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000008:administration & dosage; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D023421:Models, Animal; D053758:Nanoparticles; D014183:Transplantation, Heterologous; D014759:Viral Envelope Proteins / Q000008:administration & dosage
chemical_list: D004337:Drug Carriers; D005452:Fluoresceins; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins; C007740:fluorexon