The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection

被引：55

作者：

Kakimoto, Shinji ^{[1
]}

Hamada, Tsutomu ^{[2
]}

Komatsu, Yuuki ^{[2
]}

Takagi, Masahiro ^{[2
]}

Tanabe, Toshizumi ^{[1
]}

Azuma, Hideki ^{[1
]}

Shinkai, Seiji ^{[3
,4
]}

Nagasaki, Takeshi ^{[1
]}

机构：

[1] Osaka City Univ, Grad Sch Engn, Dept Appl Chem & Bioengn, Sumiyoshi Ku, Osaka 5588585, Japan

[2] Japan Adv Inst Sci & Technol, Sch Mat Sci, Nomi, Ishikawa 9231292, Japan

[3] Kyushu Univ, Grad Sch Engn, Dept Chem & Biochem, Nishi Ku, Fukuoka 8190395, Japan

[4] Kyushu Univ, Ctr Future Chem, Nishi Ku, Fukuoka 8190395, Japan

来源：

BIOMATERIALS | 2009年 / 30卷 / 03期

关键词：

Gene transfer; Controlled drug release; Protein; Nanocomposite; MEMBRANE TRANSLOCATION; DELIVERY-SYSTEMS; LIPID VESICLES; PORE FORMATION; CELLS; PEPTIDES; DNA; TRANSFERRIN; CULTURE; ENTRY;

D O I：

10.1016/j.biomaterials.2008.09.042

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency. On the other hand, the diphtheria toxin T domain fuses with endosome membrane by pH decrease, then enhances the endosomal escape of the diphtheria toxin C fragment. In this study, we constructed diphtheria toxin T domain-conjugated poly(ethylenimine)s (PEI) polyplex for enhancing the endosomal escape of exogenous gene. The conjugation of diphtheria toxin T domain with PEI/pDNA polyplex leads to the significant enhancement of transfection efficiency when compared with plain PEI/pDNA polyplex. The pH-responsive increase in hydrophobicity of the diphtheria toxin T domain might not only trigger the perturbation of the endocytic vesicle membrane but might also increase the membrane permeability. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：402 / 408

页数：7

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