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

• Main Authors: Suntharalingam, Kogularamanan (Contributor), Lippard, Stephen J. (Contributor), Zheng, Yaorong (Contributor), Johnstone, Timothy (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: Royal Society of Chemistry, The, 2015-02-24T20:19:59Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Grant CA034992)
David H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Program (Kathy and Curt Marble Cancer Research Fund)
National Institutes of Health (U.S.) (Grant 1S10RR13886-01)