In Vitro and In Vivo gene delivery mediated by Lactosylated Dendrimer/α-Cyclodextrin Conjugates (G2) into Hepatocytes

被引：76

作者：

Arima, Hidetoshi ^{[1
]}

Yamashita, Shogo ^{[1
]}

Mori, Yoshimasa ^{[1
]}

Hayashi, Yuya ^{[1
]}

Motoyama, Keiichi ^{[1
]}

Hattori, Kenjiro ^{[2
]}

Takeuchi, Tomoko ^{[2
]}

Jono, Hirofumi ^{[3
]}

Ando, Yukio ^{[3
]}

Hirayama, Fumitoshi ^{[4
]}

Uekama, Kaneto ^{[4
]}

机构：

[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan

[2] Tokyo Inst Polytech, Fac Engn, Dept Appl Chem, Atsugi, Kanagawa 2430297, Japan

[3] Kumamoto Univ, Grad Sch Med Sci, Kumamoto 8608556, Japan

[4] Sojo Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan

来源：

JOURNAL OF CONTROLLED RELEASE | 2010年 / 146卷 / 01期

基金：

日本学术振兴会;

关键词：

Non-viral vector; Dendrimer conjugate; alpha-Cyclodextrin; Lactose; Hepatocyte; AIRWAY EPITHELIAL-CELLS; HUMAN HEPATOMA-CELLS; TRANSFER EFFICIENCY; NUCLEAR IMPORT; POLYAMIDOAMINE DENDRIMER; BETA-CYCLODEXTRINS; MAMMALIAN-CELLS; PLASMID DNA; ASIALOGLYCOPROTEIN RECEPTOR; TRANSFECTION EFFICIENCY;

D O I：

10.1016/j.jconrel.2010.05.030

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The purpose of this study is to evaluate in vitro and in vivo gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2) conjugates with a-cyclodextrin (alpha-CDE (G2)) bearing lactose (Lac-alpha-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier in hepatocytes. Lac-alpha-CDE (DSL 2.6) was found to have much higher gene transfer activity than dendrimer, alpha-CDE, Lac-alpha-CDE (DSL 1.2, 4.6, 6.2 and 10.2) and lactosylated dendrimer (Lac-dendrimer, DSL 2.4) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R), reflecting the cellular association of the plasmid DNA (pDNA) complexes. The physicochemical properties of pDNA complex with Lac-alpha-CDE (DSL 2.6) were almost comparable to that with alpha-CDE. Lac-alpha-CDE (DSL 2.6) provided negligible cytotoxicity up to a charge ratio of 150 in HepG2 cells. Lac-alpha-CDE (DSL 2.6) provided gene transfer activity higher than jetPEI (TM)-Hepatocyte to hepatocytes with much less changes of blood chemistry values 12 h after intravenous administration in mice. These results suggest the potential use of Lac-alpha-CDE (DSL 2.6) as a non-viral vector for gene delivery toward hepatocytes. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：106 / 117

页数：12

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