Salmon calcitonin (sCT) is a therapeutic polypeptide drug widely used to treat bone diseases such as osteoporosis (more than 200 million patients all over the world). The half-life of sCT is very short (˜ 1 h), thus various delivery systems have been developed for sCT in order to avoid frequent injections. However, most delivery systems use polymeric materials, which may limit their applications in clinic formulations due to the biocompatibility issue. We observed that a very simple dipeptide (Asp-Phe, DF) was co-assembled with sCT into supramolecular nanoparticles. These nanoparticles can significantly prolong the acting time of sCT to beyond one month after just a single subcutaneous injection. The assembling and releasing mechanisms were thoroughly investigated by both in vitro and in vivo methods, as well as by molecular dynamics simulations. This work provides an alternative strategy of designing protein/peptide drug delivery systems with long-lasting therapeutic effects.Graphical abstract
Supramolecular dipeptide-calcitonin nanoparticles are prepared to prolong the acting time of calcitonin in rats to beyond one month after a single subcutaneous injection (the original half-life is about 40 min).