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

共 59 条

[1] Beta-cyclodextrin derivatives as carriers to enhance the antiviral activity of an antisense oligonucleotide directed toward a coronavirus intergenic consensus sequence [J].

Abdou, S ;

Collomb, J ;

Sallas, F ;

Marsura, A ;

Finance, C .

ARCHIVES OF VIROLOGY, 1997, 142 (08) :1585-1602

[2] Enhancement of gene expression by polyamidoamine dendrimer conjugates with α-, β-, and γ-cyclodextrins [J].

Arima, H ;

Kihara, F ;

Hirayama, F ;

Uekama, K .

BIOCONJUGATE CHEMISTRY, 2001, 12 (04) :476-484

[3] Enhancement of gene transfer activity mediated by mannosylated dendrimer/α-cyclodextrin conjugate (generation 3, G3) [J].

Arima, Hidetoshi ;

Chihara, Yuko ;

Arizono, Masayo ;

Yamashita, Shogo ;

Wada, Koki ;

Hirayama, Fumitoshi ;

Uekama, Kaneto .

JOURNAL OF CONTROLLED RELEASE, 2006, 116 (01) :64-74

[4] SERUM ALKALINE DNASE ACTIVITY IN NORMAL OR NONHOSPITALIZED INDIVIDUALS [J].

AVALLLUNDQVIST, E ;

ECONOMIDOUKARAOGLOU, A ;

SJOVALL, K ;

LANS, M ;

TAPER, HS ;

ROBERFROID, M ;

ENEROTH, P .

CLINICA CHIMICA ACTA, 1989, 185 (01) :35-43

[5]

BAENZIGER JU, 1979, J BIOL CHEM, V254, P789

[6]

Baker James R. Jr., 2004, V245, P67

[7] Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery [J].

Bellocq, NC ;

Pun, SH ;

Jensen, GS ;

Davis, ME .

BIOCONJUGATE CHEMISTRY, 2003, 14 (06) :1122-1132

[8] Size reduction of galactosylated PEI/DNA complexes improves lectin-mediated gene transfer into hepatocytes [J].

Bettinger, T ;

Remy, JS ;

Erbacher, P .

BIOCONJUGATE CHEMISTRY, 1999, 10 (04) :558-561

[9] THE H1-POLYPEPTIDES AND H2-POLYPEPTIDES ASSOCIATE TO FORM THE ASIALOGLYCOPROTEIN RECEPTOR IN HUMAN HEPATOMA-CELLS [J].

BISCHOFF, J ;

LIBRESCO, S ;

SHIA, MA ;

LODISH, HF .

JOURNAL OF CELL BIOLOGY, 1988, 106 (04) :1067-1074

[10] Synthesis, activity, and structure-activity relationship studies of novel cationic lipids for DNA transfer [J].

Byk, G ;

Dubertret, C ;

Escriou, V ;

Frederic, M ;

Jaslin, G ;

Rangara, R ;

Pitard, B ;

Crouzet, J ;

Wils, P ;

Schwartz, B ;

Scherman, D .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (02) :224-235

← 1 2 3 4 5 6 →