Elucidating the RNA Nano–Bio Interface: Mechanisms of Anticancer Poly I:C RNA and Zinc Oxide Nanoparticle Interaction
Understanding the RNA nano-bio interface is critical to advance RNA based therapeutics. A relevant RNA polyinosinic:cytidilic acid (poly I:C) is perhaps the best studied in clinical trials and is now considered an antimetastatic RNA targeting agent. Also, zinc oxide nanoparticle (ZnO NP) has well-known anticancer activity. In this work, we explore the RNA nano-bio interface of poly I:C, its mononucleotides and homopolymers with ZnO NP by UV, fluorescence and fourier transform infrared (FTIR) spectroscopies. The loading method and ionic concentration (1.0 M Na+) were optimized for greater physical association of RNA with the NP, providing greater payload (150 μg/mg NP). The physical parameters of RNA nano-bio interaction, denoting the degree of association, were quantified by modified Stern-Volmer equations (Kb = 329.6 g-1 L). This interface was further studied by two-dimensional fluorescence difference spectroscopy (2D-FDS), where greater interaction was indicated by considerable quenching of the fluorescent hot-spot. The mononucleotides and homopolymers of inosine had higher payload, binding constants, and 2D-FDS quenching, implicating the purine ring in ZnO-pIC interaction because of its greater electron density. X-ray photoelectron spectroscopy indicates the presence of RNA on the NP surface. Infrared spectral studies confirm that pIC interacts directly through inosine with the positive surface of ZnO via the carboxyl group and aromatic ring and indirectly via the phosphate group.