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

Yao Rong Zheng, Kogularamanan Suntharalingam, Timothy C. Johnstone, Stephen J. Lippard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

228 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1189-1193
Number of pages5
JournalChemical Science
Volume6
Issue number2
Early online date24 Nov 2014
DOIs
Publication statusPublished - 1 Feb 2015

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