Manipulating Immune Activation of Macrophages by Tuning the Oligonucleotide Composition of Gold Nanoparticles

This paper describes how the ligand shell containing immunostimulatory oligonucleotides surrounding gold nanoparticles affects the in vitro activation of macrophages. Nanoconstructs with similar ligand densities but different oligonucleotide compositions (from 0% to 100% immune-active cytosine-phosphate-guanine, CpG) were compared. Maximum immunostimulation was achieved with CpG content as low as 5% (with total oligonucleotide surface coverage remaining constant), correlating to high levels of antitumor cytokine release and low levels of cancer-promoting ones. Independent of CpG content, gold nanoparticles with low oligonucleotide densities exhibit poor cellular uptake, leading to insignificant immunostimulation and cytokine release. By identifying effects of ligand shell composition on macrophage activation, we can inform the design rules of therapeutic nanoconstructs to achieve specific immune responses.