This Letter describes how the endosomal organization of immunostimulatory nanoconstructs can tune the in vitro activation of macrophages. Nanoconstructs composed of gold nanoparticles conjugated with unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides have distinct endosomal distributions depending on the surface curvature. Mixed-curvature constructs produce a relatively high percentage of hollow endosomes, where constructs accumulated primarily along the interior edges. These constructs achieved a higher level of toll-like receptor (TLR) 9 activation along with the enhanced secretion of proinflammatory cytokines and chemokines compared to constant-curvature constructs that aggregated mostly in the center of the endosomes. Our results underscore the importance of intraendosomal interactions in regulating immune responses and targeted delivery.
Keywords: CpG; immunostimulation; intracellular targeting; nanoparticle; surface curvature.