Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Han, Jiaying, Rader, Andreas, Reichart, Florian, Aikman, Brech, Wenzel, Margot Nina ORCID:, 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 ORCID: 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

[thumbnail of BioconjChem_targetedPd2L4_revised_2018-10-25_final.pdf]
PDF - Accepted Post-Print Version
Download (883kB) | Preview
[thumbnail of SupportingInformation-revised_2018-10-25_final.pdf]
PDF - Supplemental Material
Download (3MB) | Preview


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: 18 May 2024 13:42

Citation Data

Cited 26 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics