Chapter 8 - Bio-nanocapsule-liposome conjugates for in vivo pinpoint drug and gene delivery

Methods Enzymol. 2009:464:147-66. doi: 10.1016/S0076-6879(09)64008-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Genetic Therapy*
  • Genetic Vectors / chemistry
  • Genetic Vectors / genetics
  • Hepatitis B virus / chemistry
  • Hepatitis B virus / genetics
  • Humans
  • Liposomes / chemistry*
  • Mice
  • Molecular Biology / methods*
  • Nanocapsules / chemistry*
  • Saccharomyces cerevisiae / genetics

Substances

  • Liposomes
  • Nanocapsules