Synthesis of antiviral nanoparticles against dengue virus

FEDERICO GIOVANNONI; ADA YESTE; LAURA B. TALARICO; FRANCISCO QUINTANA; GARCIA, CYBELE

Estambul

Workshop; ?EMBO Workshop on Human RNA Viruses?; 2014

ICGEB

At present there are neither vaccines nor therapeutic agents available to treat orprevent dengue disease, thus, the development of effective antivirals is considered of high priority.Nanomedicine has emerged as an alternative therapy for cancer and autoimmune diseases as wellas infectious diseases. Gold nanoparticles (GNPs) are widely employed due to their ease ofsynthesis, ease of functionalization, and low toxicity. These characteristics turn GNPs into anexcellent tool for drug delivery applications.In the last years our group has been studying the antiviral activity of an acridone derivative (3f).Mechanistic studies demonstrated that 3f did not affect both the initial steps of adsorption andinternalization, while the subsequent process of viral RNA synthesis was strongly inhibited. Herewe present our preliminary data about the synthesis of 3f conjugated gold nanoparticles. First, theinteraction between GNPs and the antiviral drug was confirmed via UV-visible spectradetermination, which showed a shift in the surface plasmon resonance band of GNPs after theaddition of 3f. Moreover, HPLC analysis confirmed the loading of the compound to GNPs. Drugloading percentage was estimated to be 33-40%. Transmission electron microscopy of GNPsshowed a non-aggregated, monodispersed morphology with an average diameter of 65 nm.GNPs toxicity was evaluated by the Alamarblue assay in different cell cultures, and cell viabilitywas not affected in the range of GNPs concentration tested (up to 1011 NPs/mL).Finally, the GNPs were subjected to an animal toxicity study in C57BL/6 mice. Animal survival,weight, hematology, morphology, and organ index were characterized at different concentrations(low and high dose) over 7 days.Our results show that we were able to obtain antiviral drug loaded-GNPs. Their physical andchemical properties were characterized and the first in vitro and in vivo toxicity assays showedgood perspectives as antiviral nanoparticles.