Inorganic ions as excipients for cell-penetrating peptide-mediated nucleic acid delivery

Abstract

Efficient delivery of nucleic acid-based therapeutics is a challenge that needs to be addressed. Cell-penetrating peptides (CPPs) have emerged over the years as promising vehicles for nucleic acid delivery due to their ability to traverse cell membranes, carrying cargo molecules into cells. However, such transfection still needs improvement. This study investigated how the supplementation with inorganic biocompatible ions impacts the efficacy of CPP-mediated delivery of nucleic acids. A series of salts yielding ions of interest was used. Results showed that some ions, such as Ca2+, Mg2+, PO4 3-, HPO42-, H2PO4-, and NO3-, significantly increased the biological effect of nucleic acids delivered within CPP/nucleic acid nanoparticles, while also affecting the particle size, surface charge, and stability. Understanding the role of ion supplementation provides valuable insights for the development of more effective drug delivery systems.