Impact of Sequence Specificity of Spherical Nucleic Acids on Macrophage Activation in Vitro and in Vivo

The effects of spherical nucleic acid (SNA) gold nanoparticle conjugates on the activation of macrophages in vitro and release of cytokines in vivo were explored. Herein, we show that G-quadruplexes, the formation of which is enhanced on gold nanoparticle surfaces, elicit an increase in cytokine release from mouse and human macrophages and induce the upregulation of activation receptors as well as NO₂ production in vitro. Moreover, these G-rich SNAs can induce cytokine release when injected intravenously, though there were no severe, long-term effects observed. These results further reinforce the notion that nucleic acid sequence and structure play an important role in how SNAs interact in biological milieu and highlight a key design parameter.