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Title
Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes
AuthorHeffeter, Petra, Petra ; Teasdale, Ian, Ian ; Keppler, Bernhard K. ; Berger, Walter ; Brueggemann, Oliver ; Koerner, Wilfried ; Theiner, Sarah ; Banfic, Jelena ; Kryeziu, Kushtrim ; Henke, Helena
Published in
Macromolecular Bioscience, Weinheim, 2016, Vol. 16, Issue 8, page 1239-1249
PublishedWeinheim : Wiley-Blackwell, 2016
LanguageEnglish
Document typeJournal Article
Keywords (EN)biodegradable / nanomedicine / platinum(iv) prodrugs / polymer therapeutics / polyphosphazenes / polymer therapeutics / drug-delivery / in-vitro; platinum(iv) complexes / antitumor-activity / gene delivery / polyphosphazenes / cancer / nanomedicines / opportunities
Project-/ReportnumberP 24659-N28
ISSN1616-5187
URNurn:nbn:at:at-ubmuw:3-1632 Persistent Identifier (URN)
DOI10.1002/mabi.201600035 
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Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes [1.31 mb]
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Abstract (English)

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.

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CC-BY-License (4.0)Creative Commons Attribution 4.0 International License