Effect of Confinement in Nanopores on RNA Interactions with Functionalized Mesoporous Silica Nanoparticles

Amine-functionalized mesoporous silica nanoparticles (MSNPAs) are ideal carriers for oligonucleotides for gene delivery and RNA interference. This investigation examines the thermodynamic driving force of interactions of double-stranded (ds) RNA with MSNPAs as a function of RNA length (84 and 282 base pair) and particle pore diameter (nonporous, 2.7, 4.3, and 8.1 nm) using isothermal titration calorimetry, extending knowledge of solution-based nucleic acid-polycation interactions to RNA confined in nanopores. Adsorption of RNA follows a two-step process: endothermic interactions driven by entropic contribution from counterion (and water) release and an exothermic regime dominated by short-range interactions within the pores. Evidence of hindered pore loading of the longer RNA and pore size-dependent confinement of RNA in the MSPAs is provided from the relative contributions of the endothermic and exothermic regimes. Reduction of endothermic and exothermic enthalpies in both regimes in the presence of salt for both lengths of RNA indicates the significant contribution of short-range electrostatic interactions, whereas ΔH and ΔG values are consistent with conformation changes and desolvation of nucleic acids upon binding with polycations. Knowledge of the interactions between RNA and functionalized porous nanoparticles will aid in porous nanocarrier design suitable for functional RNA delivery.