Synthesis of antiviral nanoparticles against dengue viruses

GIOVANNONI F; YESTE A; TALARICO LB; QUINTANA F; GARCÍA CC

Istanbul

Workshop; IV ICGEB Workshop on Human RNA Viruses, EMBO Workshop on Human RNA Viruses; 2014

At present there are neither vaccines nor therapeutic agents available to treat or prevent 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 well as infectious diseases. Gold nanoparticles (GNPs) are widely employed due to their ease of synthesis, ease of functionalization, and low toxicity. These characteristics turn GNPs into an excellent 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 and internalization, while the subsequent process of viral RNA synthesis was strongly inhibited. Here we present our preliminary data about the synthesis of 3f conjugated gold nanoparticles. First, the interaction between GNPs and the antiviral drug was confirmed via UV-visible spectra determination, which showed a shift in the surface plasmon resonance band of GNPs after the addition of 3f. Moreover, HPLC analysis confirmed the loading of the compound to GNPs. Drug loading percentage was estimated to be 33-40%. Transmission electron microscopy of GNPs showed 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 viability was 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 and chemical properties were characterized and the first in vitro and in vivo toxicity assays showed good perspectives as antiviral nanoparticles.