Delas Tim, Mock-Joubert Maxime, Faivre Jimmy, Hofmaier Mirjam, Sandre Olivier, Dole François, Chapel Jean Paul, Crépet Agnès, Trombotto Stéphane, Delair Thierry, Schatz Christophe
Laboratoire de Chimie des Polymères Organiques (LCPO), Univ. Bordeaux, CNRS, Bordeaux INP, UMR 5629, 33600 Pessac, France.
Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France.
Polymers (Basel). 2019 Jul 25;11(8):1236. doi: 10.3390/polym11081236.
In the context of gene delivery, chitosan has been widely used as a safe and effective polycation to complex DNA, RNA and more recently, siRNA. However, much less attention has been paid to chitosan oligosaccharides (COS) despite their biological properties. This study proposed to carry out a physicochemical study of COS varying in degree of polymerization (DP) from 5 to 50, both from the point of view of the solution properties and the complexing behavior with siRNA. The main parameters studied as a function of DP were the apparent pK, the solubility versus pH, the binding affinity with siRNA and the colloidal properties of complexes. Some parameters, like the pK or the binding enthalpy with siRNA, showed a marked transition from DP 5 to DP 13, suggesting that electrostatic properties of COS vary considerably in this range of DP. The colloidal properties of siRNA/COS complexes were affected in a different way by the COS chain length. In particular, COS of relatively high DP (≥50) were required to form small complex particles with good stability.
在基因递送领域，壳聚糖作为一种安全有效的聚阳离子被广泛用于与DNA、RNA以及最近的siRNA形成复合物。然而，尽管壳寡糖（COS）具有生物学特性，但其受到的关注却少得多。本研究旨在从溶液性质以及与siRNA的络合行为两个角度，对聚合度（DP）在5至50之间变化的COS进行物理化学研究。作为DP的函数进行研究的主要参数包括表观pK、溶解度与pH的关系、与siRNA的结合亲和力以及复合物的胶体性质。一些参数，如pK或与siRNA的结合焓，在DP从5到13时显示出明显的转变，这表明COS的静电性质在该DP范围内有很大变化。COS链长以不同方式影响siRNA/COS复合物的胶体性质。特别是，需要相对高DP（≥50）的COS来形成具有良好稳定性的小复合物颗粒。
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