A Novel, Bio-Reducible Gene Vector Containing Arginine and Histidine Enhances Gene Transfection and Expression of Plasmid DNA

被引：22

作者：

Tanaka, Ko ^{[1
]}

Kanazawa, Takanori ^{[1
]}

Ogawa, Takaya ^{[1
]}

Suda, Yumiko ^{[1
]}

Takashima, Yuuki ^{[1
]}

Fukuda, Tsunehiko ^{[2
]}

Okada, Hiroaki ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Pharmaceut Sci, Lab Pharmaceut & Drug Delivery, Tokyo 1920392, Japan

[2] Nagahama Inst Biosci & Technol, Shiga 5260829, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2011年 / 59卷 / 02期

关键词：

disulfide-cross linkage; peptide gene vector; endosomal escape; RNA INTERFERENCE; RICH PEPTIDES; IN-VITRO; MOLECULAR TRANSPORTERS; DRUG-DELIVERY; NANO DEVICE; DISEASE; SIRNA; OCTAARGININE; THERAPY;

D O I：

10.1248/cpb.59.202

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have engineered a novel, non-viral, multifunctional gene vector (STR-CH2R4H2C) that contained stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH2R4H2C can form a stable nano-complex with plasmid DNA (pDNA) based on electronic interactions and disulfide cross linkages. In this study, we evaluated the efficacy of STR-CH2R4H2C as a gene vector. We first determined the optimal weight ratio for STR-CH2R4H2C/pDNA complexes. The complexes with a weight ratio of 50 showed the highest transfection efficacy. We also examined the transfection efficacy of STR-CH2R4H2C/pDNA complexes with or without serum and compared STR-CH2R4H2C/pDNA transfection efficacy with that of Lipofectamine. Even in the presence of serum, STR-CH2R4H2C showed higher transfection efficacy than did Lipofectamine. In addition, we determined the mechanism of transfection of the STR-CH2R4H2C/pDNA complexes using various cellular uptake inhibitors and evaluated its endosomal escape ability using chloroquine. Macropinocytosis was main cellular uptake pathway of STR-CH2R4H2C/pDNA complexes. Our results suggested that STR-CH2R4H2C is a promising gene delivery system.

引用

页码：202 / 207

页数：6

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