Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes
- Author(s)
- Helena Henke, Kushtrim Kryeziu, Jelena Banfic, Sarah Theiner, Wilfried Körner, Oliver Brueggemann, Walter Berger, Bernhard Keppler, Petra Heffeter, Ian Teasdale
- Abstract
The preparation of novel macromolecular prodrugs via the conjugation of two platinum(IV) complexes to suitably functionalized poly(organo)phosphazenes is presented. The inorganic/organic polymers provide carriers with controlled dimensions due to the use of living cationic polymerization and allow the preparation of conjugates with excellent aqueous solubility but long-term hydrolytic degradability. The macromolecular Pt(IV) prodrugs are designed to undergo intracellular reduction and simultaneous release from the macromolecular carrier to present the active Pt(II) drug derivatives. In vitro investigations show a significantly enhanced intracellular uptake of Pt for the macromolecular prodrugs when compared to small molecule Pt complexes, which is also reflected in an increase in cytotoxicity. Interestingly, drug-resistant sublines also show a significantly smaller resistance against the conjugates compared to clinically established platinum drugs, indicating that an alternative uptake route of the Pt(IV) conjugates might also be able to overcome acquired resistance against Pt(II) drugs. In vivo studies of a selected conjugate show improved tumor shrinkage compared to the respective Pt(IV) complex. (Figure presented.).
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Johannes Kepler Universität Linz, Medizinische Universität Wien
- Journal
- Macromolecular Bioscience
- Volume
- 16
- Pages
- 1239-1249
- No. of pages
- 11
- ISSN
- 1616-5187
- DOI
- https://doi.org/10.1002/mabi.201600035
- Publication date
- 08-2016
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106002 Biochemistry, 106023 Molecular biology, 301206 Pharmacology
- Keywords
- ASJC Scopus subject areas
- Bioengineering, Materials Chemistry, Polymers and Plastics, Biotechnology, Biomaterials
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/macromolecular-ptiv-prodrugs-from-polyorganophosphazenes(7d93ce61-25a8-403f-9082-ffc265637f19).html