Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies

被引：67
作者：
Fernandes, Julio C. [1 ]
Qiu, Xingping [2 ]
Winnik, Francoise M. [2 ]
Benderdour, Mohamed [1 ]
Zhang, Xiaoling [3 ]
Dai, Kerong [3 ]
Shi, Qin [1 ]
机构：
[1] Univ Montreal, Sacre Coeur Hosp, Orthopaed Res Lab, Res Ctr, Montreal, PQ H4J 1C5, Canada
[2] Univ Montreal, Fac Pharm, Dept Phys Chem & Polymer Sci, Montreal, PQ H4J 1C5, Canada
[3] Shanghai Jiao Tong Univ, Sch Med, Orthopaed Cellular & Mol Biol Labs, Inst Hlth Sci,Chinese Acad Sci, Shanghai 200030, Peoples R China
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2012年 / 7卷
基金：
加拿大健康研究院; 中国国家自然科学基金;
关键词：
nonviral vector; chitosan; gene delivery; folate-targeted; siRNA; GENE DELIVERY; RNA INTERFERENCE; RECEPTOR; NANOPARTICLES; POLY(ETHYLENIMINE); EXPRESSION; EFFICIENCY; ARTHRITIS; VECTORS; THERAPY;
D O I：
10.2147/IJN.S35567
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
The low transfection efficiency of chitosan is one of its drawbacks as a gene delivery carrier. Low molecular weight chitosan may help to form small-sized polymer-DNA or small interfering RNA (siRNA) complexes. Folate conjugation may improve gene transfection efficiency because of the promoted uptake of folate receptor-bearing cells. In the present study, chitosan was conjugated with folate and investigated for its efficacy as a delivery vector for siRNA in vitro. We demonstrate that the molecular weight of chitosan has a major influence on its biological and physicochemical properties, and very low molecular weight chitosan (below 10 kDa) has difficulty in forming stable complexes with siRNA. In this study, chitosan 25 kDa and 50 kDa completely absorbed siRNA and formed nanoparticles (<220 nm) at a chitosan to siRNA weight ratio of 50:1. The introduction of a folate ligand onto chitosan decreased nanoparticle toxicity. Compared with chitosan-siRNA, folate-chitosan-siRNA nanoparticles improved gene silencing transfection efficiency. Therefore, folate-chitosan shows potential as a viable candidate vector for safe and efficient siRNA delivery.
引用
收藏
页码：5833 / 5845
页数：13
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