Effects of incorporation of poly(γ-glutamic acid) in chitosan/DNA complex nanoparticles on cellular uptake and transfection efficiency

被引：103

作者：

Peng, Shu-Fen ^{[1
]}

Yang, Mei-Ju ^{[1
,2
]}

Su, Chun-Jen ^{[1
]}

Chen, Hsin-Lung ^{[1
]}

Lee, Po-Wei ^{[1
]}

Wei, Ming-Cheng ^{[1
]}

Sung, Hsing-Wen ^{[1
]}

机构：

[1] Natl Tsing Hua Univ, Bioengn Program, Dept Chem Engn, Hsinchu 30013, Taiwan

[2] Ind Technol Res Inst, Biomed Engn Res Labs, Hsinchu, Taiwan

来源：

BIOMATERIALS | 2009年 / 30卷 / 09期

关键词：

Chitosan; Poly(gamma-glutamic acid); Transfection efficiency; Cellular uptake; MEDIATED GENE-TRANSFER; PLASMID DNA; DELIVERY; CARRIER; POLYSACCHARIDE; DEACETYLATION; PROTEOGLYCANS; ALGINATE; VECTORS;

D O I：

10.1016/j.biomaterials.2008.12.019

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Chitosan (CS)/DNA complex nanoparticles (NPs) have been considered as a vector for gene delivery. Although advantageous for DNA packing and protection, CS-based complexes may lead to difficulties in DNA release once arriving at the site of action. In this study, an approach through modifying their internal structure by incorporating a negatively charged poly(gamma-glutamic acid) (gamma-PGA) in CS/DNA complexes (CS/DNA/gamma-PGA NPs) is reported. The analysis of small angle X-ray scattering results revealed that DNA and gamma-PGA formed complexes with CS separately to yield two types of domains, leading to the formation of "compounded NPs". With this internal structure, the compounded NPs might disintegrate into a number of even smaller sub-particles after cellular internalization, thus improving the dissociation capacity of CS and DNA. Consequently, after incorporating gamma-PGA in CS/DNA complexes, a significant increase in their transfection efficiency was found. Interestingly, in addition to improving the release of DNA intracellularly, the incorporation of gamma-PGA in CS/DNA complexes significantly enhanced their cellular uptake. We further demonstrated that besides a non-specific charged-mediated binding to cell membranes, there were specific trypsin-cleavable proteins involved in the internalization of CS/DNA/gamma PGA NPs. The aforementioned results indicated that gamma-PGA played multiple important roles in enhancing the cellular uptake and transfection efficiency of CS/DNA/gamma-PGA NPs. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1797 / 1808

页数：12