Functionalization of Ruthenium(II) Terpyridine Complexes with Cyclic RGD Peptides To Target Integrin Receptors in Cancer Cells

The lack of selectivity for cancer cells and the resulting\ud negative impact on healthy tissue is a severe drawback of actual\ud cancer chemotherapy. Tethering of cytotoxic drugs to targeting\ud vectors such as peptides, which recognize receptors overexpressed\ud on the surface of tumor cells, is one possible strategy to overcome\ud such a problem. The pentapeptide cyc(RGDfK) targets the integrin\ud receptor αvβ3, important for tumor growth and metastasis formation.\ud In this work, two terpyridine based Ru(II) complexes were prepared\ud and for the first time conjugated to cyc(RGDfK) via amide bond\ud formation resulting in a monomeric and a dimeric bioconjugate. Both\ud Ru(II) complexes bind strongly and selectively to integrin αvβ3, with\ud the dimeric molecule displaying a 20-fold higher affinity to the\ud receptor than the monomeric one. However, the cytotoxicity of the\ud complexes and related bioconjugates against human A549 and\ud SKOV-3 cell lines is still not sufficient for application as anticancer\ud agents. Nevertheless, considering the high selectivity for integrin\ud receptor αvβ3, the synthesis of Ru-based bioconjugates with\ud cyc(RGDfK) paves a promising way towards the design of effective\ud targeted anticancer agents.