| RRC ID |
43847
|
| 著者 |
Somiya M, Yoshimoto N, Iijima M, Niimi T, Dewa T, Jung J, Kuroda S.
|
| タイトル |
Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B virus surface antigen L protein particles.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
We have previously demonstrated that lipoplex, a complex of cationic liposomes and DNA, could be targeted to human hepatic cells in vitro and in vivo by conjugation with bio-nanocapsules (BNCs) comprising hepatitis B virus (HBV) surface antigen L protein particles. Because the BNC-lipoplex complexes were endowed with the human hepatic cell-specific infection machinery from HBV, the complexes showed excellent specific transfection efficiency in human hepatic cells. In this study, we have found that polyplex (a complex of polyethyleneimine (PEI) and DNA) could form stable complexes with BNCs spontaneously. The diameter and ζ-potential of BNC-polyplex complexes are about 240 nm and +3.54 mV, respectively, which make them more suitable for in vivo use than polyplex alone. BNC-polyplex complexes with an N/P ratio (the molar ratio of the amine group of PEI to the phosphate group of DNA) of 40 showed excellent transfection efficiency in human hepatic cells. When acidification of endosomes was inhibited by bafilomycin A1, the complexes showed higher transfection efficiency than polyplex itself, strongly suggesting that the complexes escaped from endosomes by both fusogenic activity of BNCs and proton sponge activity of polyplex. Furthermore, the cytotoxicity is comparable to that of polyplex of the same N/P value. Thus, BNC-polyplex complexes would be a promising gene delivery carrier for human liver-specific gene therapy.
|
| 巻・号 |
20(12)
|
| ページ |
3873-9
|
| 公開日 |
2012-6-15
|
| DOI |
10.1016/j.bmc.2012.04.031
|
| PII |
S0968-0896(12)00315-X
|
| PMID |
22591855
|
| MeSH |
DNA / chemistry*
Dose-Response Relationship, Drug
Endosomes / drug effects
Gene Transfer Techniques*
Genetic Therapy
Hepatitis B Surface Antigens / chemistry*
Hepatitis B Surface Antigens / metabolism
Hepatocytes / metabolism*
Humans
Macrolides / pharmacology
Nanoparticles / chemistry*
Organ Specificity
Particle Size
Polyethyleneimine / chemistry*
Polyethyleneimine / pharmacology
Tumor Cells, Cultured
|
| IF |
3.073
|
| 引用数 |
5
|
|
WOS 分野
|
CHEMISTRY, MEDICINAL
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
