RNA-Iron Oxide Nanoparticle Flocs: A Potential Formulation for RNA-Mediated Therapy

Abstract

Nanoparticles, for selective ligand binding interface have been studied for biomolecule-based therapeutic applications. In this line, understanding metal nanoparticle-RNA interfacial interactions is crucial for improvement of RNA-based therapeutics. The current work intends to explore the interfacial interaction of RNA with iron oxide nanoparticle (FeONP) and subsequent structural modifications in RNA. The favourable entropy changes upon interaction with FeONP indicated net structural changes in the structured RNA population. This suggested multi-layered adsorption of RNA onto FeONP interface, leading to nano-corona formation. The non-two state thermodynamic transition of RNA and appearance of relatively homogenous population at higher FeONP concentration, indicated change in intra- and inter-molecular interactions. Additionally, near-UV Circular Dichroism showed significant change in RNA chirality due to base stacking. This resulted in reduced intercalation of ethidium bromide dye to the adsorbed RNA fractions found in corona, in presence of higher concentrations of FeONP. Apparently, RNA adsorbed FeONP complex provides favourable protection from RNase A-mediated degradation for a significant duration due to steric hindrance. Thus, the results provide structural intricacies of RNA adsorbed FeONP complex, and insights into its stability against nuclease activity. This can be potentially used for RNAbased therapeutic applications in biological milieu.