Chiral gold nanoparticles manipulate osteoimmune microenvironment via macrophage autophagy for bone regeneration

The immune microenvironment orchestrates bone regeneration, which can be manipulated by macrophage autophagy. Herein, gold nanoparticles with L/D (left-handed or right-handed)-chirality (L/D-AuNPs) were synthesized with chiral glutathione ligands to stereoselectively regulate macrophage autophagy, and further manipulate immune microenvironment for bone regeneration. Notably, L-AuNPs exhibited superior macrophage uptake efficiency and higher autophagy level compared to D-AuNPs. Meanwhile, L-AuNPs improved the osteogenic microenvironment, further promoting bone regeneration. In addition, the in vivo results showed that the healing of skull defect was significantly enhanced by L-AuNPs. These findings demonstrated that chiral AuNPs can stereoselectively regulate macrophage autophagy and open an avenue for applications of chiral nanoparticles in osteoimmunity.