Antibody-Mimicking Nanocluster Ameliorates Osteoporosis in Preclinical Model

Abstract Osteoporosis occurs due to the synergistic effect of increased bone resorption and decreased bone formation. However, a therapeutic approach that can simultaneously inhibit osteoclastic resorption and promote osteogenic activity directly is still lacking. Growing evidence demonstrates the I-kappaB kinase beta (IKKβ)-mediated NF-κB activation is a common crucial regulator in differentiation of both osteoclasts and osteoblasts. Herein, we screened a peptide-coated gold nanocluster (GA) and further disclosed that the optimized GA works like an antibody to block IKKβ activation well. The GA can simultaneously inhibit IKKβ-mediated osteoclastogenesis and enhances osteoblastic mineralization in vitro and effectively ameliorates osteoporosis in a preclinical model in a safe manner. Compared with first-line antiresorptive alendronate (ALN, suppress bone resorption only), GA significantly promotes bone formation and improves the quality of bone microarchitecture in vivo. These data suggest that antibody-like GAs hold great potential in osteoporosis therapy.