Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri - Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.
Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri - Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.
Trends Pharmacol Sci. 2021 Jun;42(6):448-460. doi: 10.1016/j.tips.2021.03.002. Epub 2021 Apr 16.
Polymer and lipid nanoparticles have been extensively used as carriers to address the biological barriers encountered in siRNA and mRNA delivery. We summarize the crucial role of nanoparticle charge and ionizability in complexing RNAs, binding to biological components, escaping from the endosome, and releasing RNAs into the cytoplasm. We highlight the significant impact of the apparent pKa of nanoparticles on their efficacy and toxicity, and the importance of optimizing pKa in the development of lead formulations for RNAs. We also discuss the feasibility of fine-tuning the pKa in nanoparticles and the applications of this approach in the optimization of delivery systems for RNAs.
聚合物和脂质纳米粒已被广泛用作载体，以解决 siRNA 和 mRNA 递送上遇到的生物学屏障。我们总结了纳米颗粒的电荷和离解度在与 RNA 复合、与生物成分结合、从内涵体逃逸以及将 RNA 释放到细胞质中的关键作用。我们强调了纳米颗粒表观 pKa 对其功效和毒性的重大影响，以及优化 pKa 在 RNA 先导制剂开发中的重要性。我们还讨论了在纳米颗粒中精细调整 pKa 的可行性，以及这种方法在优化 RNA 递送系统中的应用。
