Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis

Add time:07/20/2019    Source:sciencedirect.com

The high level of bone metabolism associated with osteopenia and multifocal skeletal fracture remains a challenging clinical problem in osteoporosis patients. Salmon calcitonin (sCT), as a peptide medicine, is able to inhibit osteoclast activity and stimulate osteoblast growth. However, calcitonin receptors (CTRs) are widely distributed in vivo, limiting the specificity and therapeutic effects. Here, we report a bone-seeking hexapeptide (Asp6)-conjugated sCT (sCT-Mal-Asp6) for the targeted treatment of osteoporosis. The sCT-Mal-Asp6 was synthesized via a disulfide re-bridge reaction with high specificity and purity. It was demonstrated that the adsorption of sCT-Mal-Asp6 on hydroxyapatite (HA) was about 5.4 times higher than that of sCT. It was demonstrated a prolonged circulation time and 3-fold higher femur tissue accumulation of sCT-Mal-Asp6. In ovariectomized (OVX) models, sCT-Mal-Asp6 significantly increased the ability to attenuate hypercalcemia and reconstruct the trabecula. Our work provides an efficient approach to targeted and effective osteoporosis treatment.

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