2019 Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis

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

Instituts:
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

Abstract:
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.