| RRC ID |
37496
|
| 著者 |
Somiya M, Sasaki Y, Matsuzaki T, Liu Q, Iijima M, Yoshimoto N, Niimi T, Maturana AD, Kuroda S.
|
| タイトル |
Intracellular trafficking of bio-nanocapsule-liposome complex: Identification of fusogenic activity in the pre-S1 region of hepatitis B virus surface antigen L protein.
|
| ジャーナル |
J Control Release
|
| Abstract |
Bio-nanocapsules (BNCs) are a hollow nanoparticle consisting of about 100-nm liposome (LP) embedding about 110 molecules of hepatitis B virus (HBV) surface antigen (HBsAg) L protein as a transmembrane protein. Owing to the human hepatocyte-recognizing domains on the N-terminal region (pre-S1 region), BNCs have recently been shown to attach and enter into human hepatic cells using the early infection mechanism of HBV. Since BNCs could form a complex with an LP containing various drugs and genes, BNC-LP complexes have been used as a human hepatic cell-specific drug and gene-delivery system in vitro and in vivo. However, the role of BNCs in cell entry and intracellular trafficking of payloads in BNC-LP complexes has not been fully elucidated. In this study, we demonstrate that low pH-dependent fusogenic activity resides in the N-terminal part of pre-S1 region (NPLGFFPDHQLDPAFG), of which the first FF residues are essential for the activity, and which facilitates membrane fusion between LPs in vitro. Moreover, BNC-LP complexes can bind human hepatic cells specifically, enter into the cells via clathrin-mediated endocytosis, and release their payloads mostly into the cytoplasm. Taken together, the BNC portion of BNC-LP complexes can induce membrane fusion between LPs and endosomal membranes under low pH conditions, and thereby facilitate the endosomal escape of payloads. Furthermore, the fusogenic domain of the pre-S1 region of HBsAg L protein may play a pivotal role in the intracellular trafficking of not only BNC-LP complexes but also of HBV.
|
| 巻・号 |
212
|
| ページ |
10-8
|
| 公開日 |
2015-8-28
|
| DOI |
10.1016/j.jconrel.2015.06.012
|
| PII |
S0168-3659(15)00619-7
|
| PMID |
26074149
|
| MeSH |
Animals
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
Endocytosis
Humans
Liposomes
Mice
Nanocapsules / administration & dosage*
Saccharomyces cerevisiae*
Viral Envelope Proteins / chemistry*
|
| IF |
7.727
|
| 引用数 |
14
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
CHEMISTRY, MULTIDISCIPLINARY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-1(RCB0143) |
