Synthesis and in vivo anticancer evaluation of poly(organo)phosphazene-based metallodrug conjugates
- Hackl, Carmen M. (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Schoenhacker-Alte, Beatrix (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Heffeter, Petra (Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna)
- Kandioller, Wolfgang (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Klose, Matthias H. M. (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Henke, Helena (Institute of Polymer Chemistry, Johannes Kepler University Linz (JKU))
- Legina, Maria S. (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Jakupec, Michael A. (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Berger, Walter (Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna)
- Keppler, Bernhard K. (Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna)
- Brüggemann, Oliver (Institute of Polymer Chemistry, Johannes Kepler University Linz (JKU))
- Teasdale, Ian (Institute of Polymer Chemistry, Johannes Kepler University Linz (JKU))
DOIAbstract
Within this work we aimed to improve the pharmacodynamics and toxicity profile of organoruthenium and -rhodium complexes which had previously been found to be highly potent in vitro but showed unselective activity in vivo. Different organometallic complexes were attached to a degradable poly(organo)phosphazene macromolecule, prepared via controlled polymerization techniques. The conjugation to hydrophilic polymers was designed to increase the aqueous solubility of the typically poorly soluble metal-based half-sandwich compounds with the aim of a controlled, pH-triggered release of the active metallodrug. The synthesized conjugates and their characteristics have been thoroughly studied by means of 31P NMR and UV-Vis spectroscopy, ICP-MS anal...
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