当前位置: X-MOL 学术Nano Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Polyphenolic Nanoparticle Platforms (PARCELs) for In Vitro and In Vivo mRNA Delivery
Nano Letters ( IF 10.8 ) Pub Date : 2024-05-10 , DOI: 10.1021/acs.nanolett.4c01235
Yutian Ma 1 , Palas B. Tiwade 1 , Rachel VanKeulen-Miller 2 , Eshan A. Narasipura 1 , Owen S. Fenton 1
Affiliation  

Despite their successful implementation in the COVID-19 vaccines, lipid nanoparticles (LNPs) still face a central limitation in the delivery of mRNA payloads: endosomal trapping. Improving upon this inefficiency could afford improved drug delivery systems, paving the way toward safer and more effective mRNA-based medicines. Here, we present polyphenolic nanoparticle platforms (PARCELs) as effective mRNA delivery systems. In brief, our investigation begins with a computationally guided structural analysis of 1825 discrete polyphenolic structural data points across 73 diverse small molecule polyphenols and 25 molecular parameters. We then generate structurally diverse PARCELs, evaluating their in vitro mechanism and activity, ultimately highlighting the superior endosomal escape properties of PARCELs relative to analogous LNPs. Finally, we examine the in vivo biodistribution, protein expression, and therapeutic efficacy of PARCELs in mice. In undertaking this approach, the goal of this study is to establish PARCELs as viable delivery platforms for safe and effective mRNA delivery.

中文翻译:


用于体外和体内 mRNA 传递的多酚纳米颗粒平台 (PARCEL)



尽管脂质纳米颗粒 (LNP) 在 COVID-19 疫苗中成功应用,但在 mRNA 有效负载的递送方面仍然面临一个主要限制:内体捕获。改善这种低效率可以改进药物输送系统,为更安全、更有效的基于 mRNA 的药物铺平道路。在这里,我们提出多酚纳米颗粒平台 (PARCEL) 作为有效的 mRNA 递送系统。简而言之,我们的研究始于对 73 种不同小分子多酚和 25 个分子参数的 1825 个离散多酚结构数据点进行计算引导的结构分析。然后,我们生成结构多样的 PARCEL,评估其体外机制和活性,最终强调 PARCEL 相对于类似的 LNP 具有优越的内体逃逸特性。最后,我们检查了 PARCEL 在小鼠体内的生物分布、蛋白质表达和治疗效果。在采用这种方法时,本研究的目标是将 PARCEL 建立为安全有效的 mRNA 递送的可行递送平台。
更新日期:2024-05-10
down
wechat
bug