Bone-targeted pH-responsive cerium nanoparticles for anabolic therapy in osteoporosis

• DOI: 10.1016/j.bioactmat.2021.04.038
• Publication Date: 2021-05-20T11:45:43Z
• Authors: Ce Dou; Jianmei Li; Jian He; Fei Luo; Tao Yu; Qijie Dai; Yueqi Chen; Jianzhong Xu; Xiaochao Yang; Shiwu Dong
• Keywords: Teriparatide; Anabolic Agents

Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis, which function mainly through an overall inhibition osteoclast. However, not all osteoclasts "bone eaters"; preosteoclasts (pOCs) play anabolic roles in formation angiogenesis coupling with osteoblasts secreting platelet derived growth factor-BB (PDGF-BB). In this study, a bone-targeted pH-responsive nanomaterial was designed selectively eliminating mature (mOCs) without affecting pOCs. Biocompatible cerium nano-system (CNS) guided to the acidic extracellular microenvironment created by mOCs gained oxidative enzymatic activity. Oxidative CNS decreased viability accumulating intracellular reactive oxygen species enhancing calcium oscillation. Non-acid pOCs were thus preserved kept producing PDGF-BB, lead mesenchymal stem cell osteogenesis endothelial progenitor via PI3K-Akt activated focal adhesion kinase. treating osteoporotic ovariectomized mice, showed better protective effects compare current first line antiresorptive drug due marked higher level vascularization. We provided novel therapeutic strategy disorders excessive resorption.