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聚(2-恶唑啉)/saRNA 复合纳米粒用于靶向非病毒基因传递。

Poly(2-oxazoline)/saRNA Polyplexes for Targeted and Nonviral Gene Delivery.

机构信息

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom.

Department of Infectious Diseases, Imperial College London, Norfolk Place, London W21PG, United Kingdom.

出版信息

Biomacromolecules. 2023 Nov 13;24(11):5142-5151. doi: 10.1021/acs.biomac.3c00683. Epub 2023 Oct 4.

Abstract

RNA delivery has been demonstrated to be a potent method of vaccine delivery, as demonstrated by the recent success of the COVID-19 vaccines. Polymers have been shown to be effective vehicles for RNA delivery, with poly(ethylene imine) (PEI) being the current gold standard for delivery. Nonetheless, PEI has toxicity concerns, and so finding alternatives is desirable. Poly(2-oxazoline)s are a promising alternative to PEI, as they are generally biocompatible and offer a high degree of control over the polymer structure. Here, we have synthesized an ionizable primary amine 2-oxazoline and combined it with a double bond containing oxazoline to synthesize a small library of charged statistical and block copolymers. The pendant double bonds were reacted further to decorate the polymers with glucose via a thiol-ene click reaction. All polymers were shown to have excellent cell viability, and the synthesized block polymers showed promising complexation efficiencies for the saRNA, demonstrating a clear structure-property relationship. The polymer transfection potential was tested in various cell lines, and a polymer composition with an amine/glucose ratio of 9:27 has demonstrated the best transfection potential across all cell lines tested. Overall, the results suggest that block polymers with a cationic segment and high levels of glycosylation have the best complexation efficiency and RNA expression levels.

摘要

RNA 递送已被证明是一种有效的疫苗递送方法,最近的 COVID-19 疫苗的成功就证明了这一点。聚合物已被证明是 RNA 递送的有效载体,其中聚(亚乙基亚胺)(PEI)是目前递送的金标准。尽管如此,PEI 存在毒性问题,因此寻找替代品是可取的。聚(2-恶唑啉)是 PEI 的一种有前途的替代品,因为它们通常具有生物相容性,并能高度控制聚合物结构。在这里,我们合成了一种可离子化的伯胺 2-恶唑啉,并将其与含有双键的恶唑啉结合,合成了一小批带电荷的统计和嵌段共聚物库。侧挂双键进一步通过硫醇-烯点击反应与葡萄糖反应,用葡萄糖对聚合物进行了修饰。所有聚合物均显示出优异的细胞活力,合成的嵌段聚合物对 saRNA 表现出良好的复合物形成效率,表明存在明显的结构-性能关系。在各种细胞系中测试了聚合物的转染潜力,在所有测试的细胞系中,具有胺/葡萄糖比为 9:27 的聚合物组成显示出最佳的转染潜力。总的来说,结果表明,具有阳离子段和高糖基化水平的嵌段聚合物具有最佳的复合物形成效率和 RNA 表达水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41c6/10646937/e29348bd25f6/bm3c00683_0005.jpg

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