A guanidinylated bioreducible polymer with high nuclear localization ability for gene delivery systems

被引：82

作者：

Kim, Tae-il ^{[1
]}

Lee, Minhyung ^{[2
]}

Kim, Sung Wan ^{[1
,2
]}

机构：

[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA

[2] Hanyang Univ, Coll Engn, Dept Bioengn, Seoul 133791, South Korea

来源：

BIOMATERIALS | 2010年 / 31卷 / 07期

关键词：

Bioreducible polymer; Gene transfer; Guanidinylation; Cytotoxicity; Nuclear localization ability; PLASMID DNA DELIVERY; POLY(DISULFIDE AMINE); POLY(AMIDO AMINE)S; CARGO DELIVERY; TAT PEPTIDE; MICROPARTICLES; TRANSPORTERS; DEGRADATION; EFFICIENCY; CARRIERS;

D O I：

10.1016/j.biomaterials.2009.10.034

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Guanidinylated bioreducible polymer (GBP) was developed for gene delivery systems utilizing cellular penetrating ability of guanidine groups. GBP could retard pDNA from a weight ratio of 5 completely in agarose gel electrophoresis but pDNA was released from GBP polyplexes even at a weight ratio of 20 in reducing condition (2.5 mm DTT) due to their biodegradation. GBP also could construct 200 nm-sized and positively charged (similar to 30 mV) polyplex nanoparticles with pDNA. The cytotoxicity of GBP was found to be minimal and GBP showed about 8 folds improved transfection efficiency than a scaffold polymer, poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH)) and even higher transfection efficiency than PEI25k in mammalian cell lines. Its high cellular uptake efficiency (96.1%) and strong nuclear localization ability for pDNA delivery due to the structural advantage of bioreducible polymer and guanidine groups were also identified, suggesting GBP is a promising candidate for efficient gene delivery systems. (C) 2009 Elsevier Ltd. All rights reserved

引用

页码：1798 / 1804

页数：7

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