An activatable near-infrared fluorescent probe targeting CKIP-1 for monitoring osteoporosis in vivo

Abstract Osteoporosis (OP) is characterized by decreased bone mass and strength. Patients with OP have a higher risk of bone fragility and fracture. Currently, bone mineral density (BMD) determined by radioactive scanning is one of the most critical parameters applied in the clinical diagnosis and monitoring of therapeutic response in osteoporosis. However, radioactive scanning exposes the potential risks of long-time radiation damage. This calls for development of less toxic and highly sensitive molecular fluorescence imaging techniques. Currently, this is not possible because there are no effective indicators. Here, we found a negative correlation between osteoporosis and casein kinase 2-interacting protein-1 (CKIP-1, also known as PLEKHO1). This kinase was previously found to negatively regulate bone formation. Using this new biomarker, we designed an activatable near-infrared (NIR) fluorescent probe targeting CKIP-1 mRNA (NPC) with the toe-hold mediated strand displacement reaction and fuel amplification strategy. NIR fluorophore Cy5 and its quencher part BHQ3 were incorporated in the probe. The ratio of NPC probe and its fuel strand were also optimized. The designed detection system effectively visualized CKIP-1 at the cell level and in three different osteoporosis models. Results revealed that the NPC probe targeting CKIP-1 can be used to monitor changes in bone mass and therapy responses in vivo.