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This study describes a side-by-side comparison of the in vitro immunostimulatory activity of cytosine-phosphate-guanine (CpG)-conjugated gold nanoparticles. Three different gold nanoparticle cores (13 nm spheres, 50 nm spheres, and 40 nm stars) with the same CpG surface density were investigated for toll-like receptor 9 activation. For this parameter set, 13 nm spheres displayed significantly higher specificity for targeting immune receptors and larger nanoparticles (50 nm spheres and 40 nm stars) showed higher cellular uptake and higher immune activation because of off-target effects. Changes in nanoparticle size and presentation of activating ligands affect construct-induced immune responses at different levels, and care must be taken when considering practical and global design rules for CpG delivery.

Smaller CpG-Conjugated Gold Nanoconstructs Achieve Higher Targeting Specificity of Immune Activation