Chapter 8 - Bio-nanocapsule-liposome conjugates for in vivo pinpoint drug and gene delivery.
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.
Kasuya
Takeshi
T
Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
Jung
Joohee
J
Kinoshita
Rie
R
Goh
Yasumasa
Y
Matsuzaki
Takashi
T
Iijima
Masumi
M
Yoshimoto
Nobuo
N
Tanizawa
Katsuyuki
K
Kuroda
Shun'ichi
S
D000818:Animals; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000235:genetics
D008081:Liposomes; D053769:Nanocapsules