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壳聚糖-DNA 聚电解质复合物:壳聚糖特性的影响及复合物形成的机制。

Chitosan-DNA polyelectrolyte complex: Influence of chitosan characteristics and mechanism of complex formation.

机构信息

Universidad de Guadalajara, Departamento de Ingeniería Química, Blvd. M. García Barragán #1451, 44430 Guadalajara, Jalisco, Mexico; University of Bordeaux/Bordeaux INP, ENSCBP and CNRS, Laboratoire de Chimie des Polymères Organiques (UMR5629), 16 avenue Pey-Berland, Pessac 33607, France.

Universidad de Guadalajara, Departamento de Ingeniería Química, Blvd. M. García Barragán #1451, 44430 Guadalajara, Jalisco, Mexico; Centro Universitario UTEG, Departamento de Investigación, Héroes Ferrocarrileros #1325, Guadalajara, Jalisco 44460, Mexico.

出版信息

Int J Biol Macromol. 2019 Apr 1;126:1037-1049. doi: 10.1016/j.ijbiomac.2019.01.008. Epub 2019 Jan 4.

Abstract

Polyelectrolyte complexes formed between DNA and chitosan present different and interesting physicochemical properties combined with high biocompatibility; they are very useful for biomedical applications. DNA in its double helical structure is a semi-rigid polyelectrolyte chain. Chitosan, an abundant polysaccharide in nature, is considered as one of the most attractive vectors due to its biocompatibility and biodegradability. Here we study chitosan/DNA polyelectrolyte complex formation mechanism and the key factors of their stability. Compaction process of DNA with chitosan was monitored in terms of the ζ-potential and hydrodynamic radius variation as a function of charge ratios between chitosan and DNA. The influence of chitosan degree of acetylation (DA) and its molecular weight on the stoichiometry of chitosan/DNA complexes characteristics was also studied. It is shown that the isoelectric point of chitosan/DNA complexes, as well as their stability, is directly related to the degree of protonation of chitosan (depending on pH), to the DA and to the external salt concentration. It is demonstrated that DNA compaction process corresponds to an all or nothing like-process. Finally, since an important factor in cell travelling is the buffering effect of the vector used, we demonstrated the essential role of free chitosan on the proton-sponge effect.

摘要

DNA 与壳聚糖之间形成的聚电解质复合物结合了高生物相容性和不同的有趣物理化学性质;它们非常适用于生物医学应用。在其双螺旋结构中,DNA 是一种半刚性聚电解质链。壳聚糖是自然界中丰富的多糖,由于其生物相容性和可生物降解性,被认为是最有吸引力的载体之一。在这里,我们研究了壳聚糖/DNA 聚电解质复合物的形成机制及其稳定性的关键因素。通过测量 ζ 电势和水动力半径随壳聚糖与 DNA 之间电荷比的变化,监测了 DNA 与壳聚糖的压缩过程。还研究了壳聚糖的乙酰化程度 (DA) 和分子量对壳聚糖/DNA 复合物特性的化学计量比的影响。结果表明,壳聚糖/DNA 复合物的等电点及其稳定性与壳聚糖的质子化程度(取决于 pH 值)、DA 和外部盐浓度直接相关。结果表明,DNA 压缩过程对应于全有或全无的过程。最后,由于载体的缓冲作用是细胞迁移的一个重要因素,我们证明了游离壳聚糖在质子海绵效应中的重要作用。

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