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开发和特征改性基托桑脂聚复合物,以提供有效的siRNA输送

Shibani Supe¹, Archana Upadhya², Vikas Dighe³

¹Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS, Mumbai, 400056, Maharashtra, India.

AAPS PharmSciTech

|January 9, 2024

概括

素-氨酸复合物通过增强细胞吸收和封装来改善siRNA的传递. 与现有方法相比,脂涂复合物显示出降低的毒性和优异的基因传输.

科学领域:

生物材料科学生物材料科学
纳米技术纳米技术
基因传递基因传递

背景情况:

RNA干扰 (RNAi) 疗法面临的挑战包括细胞毒性,快速降解和细胞吸收不良.
奇托 (Cs) 是一种生物相容和生物降解的聚合物,适合siRNA输送.
修改基托与氨酸增强其siRNA封装和细胞吸收能力.

研究的目的:

开发和表征素-氨酸 (CsAr) 复合体,以改善siRNA递送.
将CsAr-siRNA复合体封装在阳离子脂质体内,创建脂质复合体 (LCAr).
评估LCAr在基因传输中的有效性,稳定性和安全性.

主要方法:

奇托被阿尔金因修改,以创建CsAr复合体.
福利埃变换红外光谱法 (FTIR) 和13C核磁共振被用于表征.
CsAr-siRNA复合体被封装在DPPC/胆固醇脂质体中,形成LCAr.
阿加罗斯凝电泳评估了复杂的形成,稳定性和siRNA封装效率.
细胞吸收和血液溶解潜力与父多复合体和Lipofectamine 2000进行了比较.

主要成果:

脂质质量比为10导致CsAr-siRNA复合体的完全脂化,形成LCAr (120-230nm).
siRNA封装量从多复合体的70%增加到LCAr的95%.
与父多复合体相比,LCAr显示出大约4倍低的溶血潜力.
与Lipofectamine 2000相比,LCAr显示细胞关联增强.

结论:

与脂质体的奇托-氨酸结合提供了一个简单,安全和强大的基因传递载体.
LCAr有效地增强了siRNA封装和细胞对基因传输的吸收.
这种新的脂聚复合系统为在生理条件下siRNA传递提供了一个有希望的替代方案.

关键词:

在阿根廷,阿根廷人.基多酸盐的使用方法脂多多复合体的复合体.视网膜细胞视网膜细胞 siRNA 是一个RNA.

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siRNA - Small Interfering RNAs

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...