Efficient Nonviral Gene Therapy Using Folate-Targeted Chitosan-DNA Nanoparticles In Vitro.

ISRN Pharmaceutics Pub Date : 2012-01-01 Epub Date: 2012-03-07 DOI:10.5402/2012/369270
Christian Jreyssaty, Qin Shi, Huijie Wang, Xingping Qiu, Françoise M Winnik, Xiaoling Zhang, Kerong Dai, Mohamed Benderdour, Julio C Fernandes
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引用次数: 18

Abstract

Nonviral cationic polymers like chitosan can be combined with DNA to protect it from degradation. The chitosan is a biocompatible, biodegradable, nontoxic, and cheap polycationic polymer with low immunogenicity. The objective of this study was to synthesize and then assess different chitosan-DNA nanoparticles and to select the best ones for selective in vitro transfection in human epidermoid carcinoma (KB) cell lines. It revealed that different combinations of molecular weight, the presence or absence of folic acid ligand, and different plasmid DNA sizes can lead to nanoparticles with various diameters and diverse transfection efficiencies. The intracellular trafficking, nuclear uptake, and localization are also studied by confocal microscopy, which confirmed that DNA was delivered to cell nuclei to be expressed.

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体外利用叶酸靶向壳聚糖- dna纳米颗粒进行有效的非病毒基因治疗。
壳聚糖等非病毒阳离子聚合物可以与DNA结合,防止DNA降解。壳聚糖是一种生物相容性、可生物降解、无毒、廉价的低免疫原性聚阳离子聚合物。本研究的目的是合成不同的壳聚糖- dna纳米颗粒并对其进行评价,并筛选出最佳的壳聚糖- dna纳米颗粒,用于体外选择性转染人表皮样癌(KB)细胞。结果表明,不同的分子量组合、叶酸配体的存在或不存在以及不同的质粒DNA大小可以导致不同直径和不同转染效率的纳米颗粒。通过共聚焦显微镜研究了细胞内运输、核摄取和定位,证实了DNA被传递到细胞核中进行表达。
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