Half‐Sandwich Ruthenium(II) Biotin Conjugates as Biological Vectors to Cancer Cells |
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| Authors: | Dr Maria V Babak Dr Damian Pla?uk Dr Samuel M Meier Homayon John Arabshahi Dr Jóhannes Reynisson Dr B?a?ej Rychlik Dr Andrzej B?au? Katarzyna Szulc Dr Muhammad Hanif Sebastian Strobl Alexander Roller Prof?Dr Bernhard K Keppler Prof?Dr Christian G Hartinger |
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| Institution: | 1. Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna (Austria);2. Research Platform, “Translational Cancer Therapy Research”, University of Vienna, Waehringer Strasse 42, 1090 Vienna (Austria);3. School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand) http://hartinger.wordpress.fos.auckland.ac.nz/;4. Department of Organic Chemistry, Faculty of Chemistry, University of ?ód?, Tamka 12, 91‐403 ?ód? (Poland);5. Institute of Analytical Chemistry, University of Vienna, Waehringer Strasse 38, 1090 Vienna (Austria);6. Cytometry Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of ?ód?, 12/16 Banacha St., 90‐237 ?ód? (Poland) |
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| Abstract: | 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 RuII–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. |
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| Keywords: | antitumor agents cancer drug delivery ruthenium sandwich complexes |
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