Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis

Imbalance between osteoblasts and osteoclasts accounts for the incidence and deterioration of postmenopausal osteoporosis. Abnormally elevated RANKL and TNF-alpha levels after menopause promote osteoclast formation and inhibit osteoblast differentiation, respectively. Here, nanodecoys capable of scavenging RANKL and TNF-alpha were developed from preosteoclast (RAW 264.7 cell) membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which inhibited osteoporosis and maintained bone integrity. The nanodecoys effectively escaped from macrophage capture and enabled prolonged blood circulation after systemic administration. The abundant RANK and TNF-alpha receptor (TNF-alpha R) on the cell membranes effectively neutralized RANKL and TNF-alpha to prevent osteoclastogenesis and promote osteoblastogenesis, respectively, thus reversing the progression of osteoporosis in the ovariectomized (OVX) mouse model. These biomimetic nanodecoys provide an effective strategy for reconstructing the osteoclast/osteoblast balance and hold great potentials for the clinical management of postmenopausal osteoporosis.