Development and in vivo analysis of antigen-mimicking monolayer-protected gold nanoparticles

Abstract

Monolayer-protected gold nanoparticles (AuNPs) have been the subject of much attention because of the simplicity of their synthesis, their stability, and the ease of functionalization via simple place-exchange reactions. Depending on the capping ligand, AuNPs can be made water-soluble and their circulation half-life in vivo can be tuned. Multiple biologically relevant molecules can be easily attached to the particle surface. These attributes make AuNPs an excellent candidate for drug delivery agents. We have developed and tested in murine models several nanoparticle scaffolds with various monolayer compositions: tiopronin, tiopronin-PEG mixed-monolayer, glutathione (GSH), and tiopronin conjugated to ethylene glycol (TioEG). Additionally, we have functionalized GS AuNPs and TioEG monolayer-protected clusters (MPCs) with a looped or linear synthetic peptide epitope from the protective antigen (PA) of B. anthracis, or anthrax, to determine if vaccinated mice responded with anti-PA antibodies. Enzyme-linked immunosorbent assay (ELISA) was used to assess antibody production, and yielded results suggestive of the presence of antibodies in the sera of mice inoculated with loop PA on TioEG MPCs at a confidence interval of 99% (p=0.0093).