Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery;
however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we
conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable selfassembled
monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate
systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer
on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA
content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpGAuNPs
were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG
modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor
growth, and promoted survival in mice when compared to treatments with free CpG