General Research Article

聚乙二醇-癸二酸作为β-环糊精-聚轮烷的骨干的生物可降解聚酯:一个有前途的基因沉默载体。

卷 19, 期 4, 2019

页: [274 - 287] 页: 14

弟呕挨: 10.2174/1566523219666190808094225

价格: $65

摘要

背景:聚轮烷是一种由环糊精组成的大分子互锁组件,具有出色的包合能力和功能化能力,使其成为基因递送应用的通用载体。 目的:以聚乙二醇(PEG)和癸二酸(SA)组成的可生物降解的线性脂族聚酯轴为原料,制备基于β-环糊精(β-CD)的聚轮烷作为阳离子聚合物载体,并对其潜在的基因沉默效率进行了评估。 方法:采用溶剂酯化法合成水溶性脂肪族聚酯,并通过粘度法,GPC,FT-IR和1H NMR表征。进一步评估了合成聚酯的生物降解性和细胞毒性。因此,该水溶性聚酯通过穿线和封端反应用于聚轮烷的逐步合成。 β-CD在PEG-SA聚酯轴上的穿线在水中进行,然后使用2,4,6-三硝基苯磺酸将聚伪轮烷封端,得到聚酯基聚轮烷。对于基因传递应用,合成了阳离子聚轮烷(PRTx +)并评估了其基因加载和基因沉默效率。 结果与讨论:发现所得的新型大分子组装物可安全用于生物医学应用。此外,通过GPC和1H NMR技术表征表明,成功形成了PE-β-CD-PRTx,穿线效率为16%。此外,细胞毒性实验表明合成的聚轮烷具有生物安全性,探索了其在基因递送和其他生物医学应用中的潜力。此外,通过测量它们的ζ电位和基因沉默效率来评估PRTx +:siRNA复合物的生物学特性,发现其与商业转染剂Lipofectamine 3000相当。结论:聚乙二醇-癸二酸基β-环糊精-聚轮烷的生物降解性,良好的络合能力,接近零的ζ电势,良好的细胞毒性等多种因素的综合作用使其成为治疗应用的有希望的基因载体。

关键词: 聚酯,环糊精,聚轮烷,生物降解,siRNA,GFP,基因沉默。

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