Ruthenium(II)-arene complexes with
biotin-containing
ligands were prepared so that a novel drug delivery system based on
tumor-specific
vitamin-receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in
cancer cell lines with various levels of major
biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the
ligands. In all cases, coordination of
ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru(II) -
biotin complexes to
avidin was investigated and was lower than that of unmodified
biotin. Hill coefficients in the range 2.012-2.851 suggest strong positive cooperation between the complexes and
avidin. To estimate the likelihood of binding to the
biotin receptor/transporter, docking studies with
avidin and
streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half-sandwich
ruthenium(II)-
biotin conjugates may act as
biological vectors to
cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the
biotin moiety was observed.