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Bioconjugation of supramolecular metallacages to integrin ligands for targeted delivery of cisplatin

Han, Jiaying, Rader, Andreas, Reichart, Florian, Aikman, Brech, Wenzel, Margot Nina, Woods, Ben, Weinmüller, Michael, Ludwig, Beatrice S., Sturup, Stefan, Groothuis, Geny M.M., Permentier, Hjalmar P., Bischoff, Rainer, Kessler, Horst, Horvatovich, Péter and Casini, Angela 2018. Bioconjugation of supramolecular metallacages to integrin ligands for targeted delivery of cisplatin. Bioconjugate Chemistry 29 (11) , pp. 3856-3865. 10.1021/acs.bioconjchem.8b00682
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Abstract

Cisplatin occupies a crucial role in the treatment of various malignant tumours. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing αvβ3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity towards healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that encapsulated drug is less accumulated in these organs compared to the ‘free’ one.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: American Chemical Society
ISSN: 1043-1802
Date of First Compliant Deposit: 12 November 2018
Date of Acceptance: 26 October 2018
Last Modified: 03 Jul 2019 11:04
URI: http://orca.cf.ac.uk/id/eprint/116658

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