The Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA

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.

Automated summary

Polymer and lipid nanoparticles play a crucial role in delivering siRNA and mRNA by interacting with biological barriers. The charge and ionizability of nanoparticles are important in complexing RNAs, escaping from endosomes, and releasing RNAs into the cytoplasm. Optimizing the apparent pKa of nanoparticles is key in developing effective and safe formulations for RNA delivery.