2019 Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis

Yanpeng Liu a, Peng Yu a, Xu Peng b, Qin Huang a,  Mingming Ding a,  Yantao Chen c, Ruitao Jin a, Jing Xie a, Changsheng Zhao a, JianshuLi a

Journal of Controlled Release, Volume 304, 28 June 2019,  https://doi.org/10.1016/j.jconrel.2019.04.042

a College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
b Laboratory Animal Center of Sichuan University, Chengdu 610041, China
c Shenzhen Key Laboratory of Environmental Chemistry and Ecological Remediationering, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China

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.