基于cationic血清的双子表面活性剂:单烯聚合物作为DNA复杂化和紧缩的可行和有效剂:细胞毒性和物理化学评估
Isabel S Oliveira1, Sandra G Silva2, Andreia C Gomes3
1CIQUP (Centro de Investigação em Química da Universidade do Porto), IMS (Institute of Molecular Sciences), Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
Journal of functional biomaterials
|August 28, 2024
概括
基于氨酸的双子表面活性剂与单氨酸混合,显示出有效的DNA复杂化,用于基因传递. 该 (18Ser) 2N5:单烯混合物表现出优异的性能和非细胞毒性,为先进的非病毒载体铺平了道路.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 分子生物学分子生物学
背景情况:
- 电离双子表面活性剂由于静电DNA复杂化而被探索为基因传递剂.
- 辅助脂质 (HL) 在非病毒载体中增强DNA复杂化和转染效率.
- 脂质斑形成取决于表面活性剂:HL比率和形态学等参数.
研究的目的:
- 为了研究基氨酸基基双子表面活性剂 ((nSer) 2N5) 与单素 (MO) 作为辅助脂质的DNA复杂化.
- 评估表面活性剂链长度和MO含量对聚合物特性和非细胞毒性的影响.
- 了解这些混合聚合物的结构特征,以了解潜在的脂质积形成.
主要方法:
- 合成基于氨酸的双子表面活性剂,具有不同的脂友链长度.
- 杰米尼表面活性剂的制备和表征:单烯混合物.
- 使用各种物理化学参数评估DNA复杂化能力.
- 使用细胞活力试验评估细胞毒性.
- 混合聚合物的形态分析使用诸如cryo-TEM (隐含) 等技术.
主要成果:
- (nSer) 2N5:MO聚合物表现出非细胞毒性,具有更高的MO含量和更长的表面活性剂链,一般改善细胞活力.
- 所有测试的系统都有效地复杂化了DNA,其中 (18Ser) 2N5:MO系统表现最好.
- 加入MO会影响混合聚合物的形态和尺寸分布,在低度形成囊泡,在高度形成状液晶相.
结论:
- 基于氨酸的双子座表面活性剂与单质素相结合,是有前途的非病毒基因传递剂.
- 该 (18Ser) 2N5:MO系统提供了DNA复杂化,低细胞毒性和可调整形态的有利平衡.
- 在双子MO聚合物中观察到的基于双层的结构表明与脂质复合体有相似之处,有助于理解非病毒载体设计.
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