Hetero-Functionalized Gold Nanoparticles to Silence AU-Rich Element Containing mRNAs in RAGE-Expressing Inflammatory...

Diabetes, a chronic metabolic disorder associated with significantly accelerated rates of inflammation. Gold nanoparticle plays a crucial role in biomedical applications. We described the development of hetero-functionalized gold nanoparticles (hfAuNPs) for targeted selective gene silencing by RNAi interference. This hfAuNPs was developed by parallelly conjugating biotinylated ARE-siRNA (siRNA to Adenosine Uridine-rich elements) and biotinylated RAGE interacting-peptide (RIP) to streptavidin coated gold nanoparticles (aAuNPs) thus forms a complex that provides biocompatibility and functionality in a physiological environment. RIP can function as targeting agent and ARE-siRNA involve in silencing ARE containing proinflammatory cytokine/chemokine and related molecules mRNAs. Characterization of nanoparticle was performed by UV-Vis spectrophotometry, fourier transform infrared spectroscopy (FTIR), dynamic light scattering, zeta potential, field emission-scanning electron microscope with energy dispersive spectrometer (FE-SEM with EDS) and atomic force microscope analysis (AFM). Plasmonic emission spectra of hfAuNPs and aAuNPs showed spectra at 275 nm and 235 nm respectively. Interestingly spectra shift from 235 nm to 275 nm proved presence of functionalized molecules in hfAuNPs. FTIR showed the hfAuNPs peak at 3338 cm-1 conveying combined O-H and N-H vibrations of streptavidin and biotin in the infrared spectra. The spherical morphology and Au presence were analyzed by FE-SEM with EDS. A complex formation was confirmed by a decrease in size and a change in zeta potential of hfAuNPs. AFM showed an increased surface roughness of hfAuNPs. The comparison of our initial in-vitro studies suggested the significant increased cellular uptake of hfAuNPs in RAGE overexpressing HeLa cells. Thus hfAuNPs could serve as novel therapeutic candidates to alleviate inflammatory disease like diabetes.