Enantiomer-dependent immunological response to chiral nanoparticles

Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.