壳聚糖及其衍生物在基因治疗应用中的研究进展

Progress in application of chitosan and its derivatives in gene therapy

壳聚糖是一种天然离子型聚合物,是天然多糖中惟一的碱性多糖。由于壳聚糖分子结构中大量游离氨的存在,使其成为了天然的少有的聚阳离子,在其分子链上有许多特殊的功能团。壳聚糖不溶于水而溶于稀酸溶液,可根据需要对壳聚糖进行化学修饰。壳聚糖及其衍生物由于具有良好的可生物降解性、生物相容性、低毒性、黏膜吸附性、免疫刺激活性、缓释、控释作用和靶向性等优点,已成为了递送基因的优良载体。本文就壳聚糖及其衍生物的理化性质及其在基因治疗中的应用和作用机制做一综述。

Chitosan is a polysaccharide derived by deacetylation of chitin.It is a kind of alkalescence amylose that exists in the nature exclusively.Non-viral vectors have been widely proposed as safer alternatives to viral vectors.Among non-viral vectors,chitosan has been considered to be a good candidate of gene carrier by reason of unique advantages such as biodegradability,biocompatibility,low toxicity,mucosa adhesion,immune stimulating activity,sustained and controlled release,and cell / tissue targeting.In addition,chitosan has cationic characters even in neutral condition to form complexes with negatively charged plasmid DNA,and promotes cell transfection.However,most of the activities are limited to acidic conditions because of its poor solubility above pH 6.5,where chitosan starts to lose its cationic nature.The poor solubility of chitosan limits its biomedical applications,so some chemical modifications are needed according to the actual needs.Here we reviewed the physic-chemical properties,application and mechanisms of chitosan,and its derivatives in gene therapy.