Kasuya Takeshi, Jung Joohee, Kinoshita Rie, Goh Yasumasa, Matsuzaki Takashi, Iijima Masumi, Yoshimoto Nobuo, Tanizawa Katsuyuki, Kuroda Shun'ichi
Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
Methods Enzymol. 2009;464:147-66. doi: 10.1016/S0076-6879(09)64008-8.
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.
生物纳米胶囊（BNC）是一种约50纳米的乙型肝炎病毒（HBV）亚病毒颗粒，由HBV包膜L蛋白和脂质双层组成，在重组酿酒酵母中合成。当在小鼠异种移植模型中静脉注射BNC时，它们可以特异性地积聚在人肝衍生组织中，并通过位于L蛋白外膜前S区域的HBV衍生的人肝特异性感染机制有效地进入细胞。通过使用靶向分子（例如抗体、凝集素、细胞因子）替代前S区域，可以将BNC对人肝脏的特异性改变为对其他组织的特异性。BNC可以通过前S区域的膜融合活性与脂质体（LP）自发形成复合物。因此，含有各种治疗物质（例如化学物质、蛋白质、DNA、RNA）的LP可以被BNC覆盖，形成约150纳米的BNC-LP缀合物。静脉注射的BNC-LP缀合物可以通过利用HBV衍生的感染机制将掺入的物质特异性且高效地递送至靶组织。BNC-LP缀合物在血液循环中的稳定性与聚乙二醇化LP的稳定性相似。在本章中，我们描述了BNC-LP缀合物的制备及其体内应用，以及BNC-LP缀合物作为体内精准给药系统的潜力。
