Issue 2, 2015

Encapsulation of Pt(iv) prodrugs within a Pt(ii) cage for drug delivery

Abstract

This report presents a novel strategy that facilitates delivery of multiple, specific payloads of Pt(IV) prodrugs using a well-defined supramolecular system. This delivery system comprises a hexanuclear Pt(II) cage that can host four Pt(IV) prodrug guest molecules. Relying on host–guest interactions between adamantyl units tethered to the Pt(IV) molecules and the cage, four prodrugs could be encapsulated within one cage. This host–guest complex, exhibiting a diameter of about 3 nm, has been characterized by detailed NMR spectroscopic measurements. Owing to the high positive charge, this nanostructure exhibits high cellular uptake. Upon entering cells and reacting with biological reductants such as ascorbic acid, the host–guest complex releases cisplatin, which leads to cell cycle arrest and apoptosis. The fully assembled complex displays cytotoxicity comparable to that of cisplatin against a panel of human cancer cell lines, whereas the cage or the Pt(IV) guest alone exhibit lower cytotoxicity. These findings indicate the potential of utilising well-defined supramolecular constructs for the delivery of prodrug molecules.

Graphical abstract: Encapsulation of Pt(iv) prodrugs within a Pt(ii) cage for drug delivery

Supplementary files

Article information

Article type
Edge Article
Submitted
25 jún. 2014
Accepted
08 okt. 2014
First published
24 nóv. 2014
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2015,6, 1189-1193

Author version available

Encapsulation of Pt(IV) prodrugs within a Pt(II) cage for drug delivery

Y. Zheng, K. Suntharalingam, T. C. Johnstone and S. J. Lippard, Chem. Sci., 2015, 6, 1189 DOI: 10.1039/C4SC01892C

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