Nerve growth factor-loaded biomimetic prussian blue nanocomplexes for reversing osteoporosis via promoting osteoblast precursor cell proliferation and differentiation

The fundamental issue of osteoporosis (OP) is osteoblast decrease due to oxidative stress and the subsequent disruption of the osteogenic and osteoclastic dynamic balance. How to promote the proliferation and osteogenic differentiation of osteoblast precursor cells (MC3T3-E1) in an oxidative microenvironment is a great challenge for improving OP. In this study, Prussian blue nanoparticles (PB NPs) were initially functionalized with a polydopamine (PDA) coating. Nerve growth factor (NGF) was subsequently immobilized on the PDA layer, followed by the hybrid membrane coating composed of red blood cell membrane (RBCm) and MC3T3-E1 cell membrane (MC3T3m), thereby constructing a biomimetic Prussian blue nanocomplex loaded with NGF (MPDN NPs). In vitro studies have shown that the nanodrug restored the impaired proliferation viability of MC3T3-E1 cells and inhibit their apoptosis by scavenging reactive oxygen species (ROS), and further cooperate with NGF to promote osteogenic differentiation. In vivo studies have demonstrated that the nanodrug significantly inhibited bone loss and promote bone regeneration in osteoporotic mice. Moreover, this nanodrug with excellent safety both in vitro and in vivo showed the long half-life in the bloodstream and high accumulation in the bone. In summary, this strategy addresses the fundamental issue of decreased osteoblast in OP and offers a novel approach for preventing and treating OP.