Hiding a potent, but insoluble, anticancer drug inside a cage complex represents a new approach to the use of inorganic chemotherapeutics
Chemotherapeutic treatments for cancer can be very effective. However, by their very nature — that is, they work by killing cells — they have some well-known and unpleasant side effects. There are a number of challenges in developing new chemotherapeutic agents, such as making them more cytotoxic and improving their selectivity so that they only target cancerous cells.
It is known that some ruthenium complexes have promising anticancer activity. Now, Bruno Therrien from the Université de Neuchâtel and co-workers1 have investigated the properties of a ruthenium cage complex. The assembly is made up of multiple metal ions connected together with organic ligands, and has a hollow cavity at its centre that can accommodate simple palladium and platinum complexes. On its own, the cage complex is mildly cytotoxic. However, when it forms a so-called complex-in-a-complex structure — by hosting the diacetylacetonate salt of either Pd or Pt in its cavity — the cytotoxicity increases dramatically. This is perhaps a surprising observation given that the Pd and Pt compounds are themselves inactive against the cancer cells, probably owing to their low water solubility.
The good solubility and large size of the highly charged ruthenium cage complex is thought to assist in its selective uptake by cancerous cells, and the ease with which the guest complex is leached from the cage is key to achieving the high cytotoxicity and selectivity. Higher activity was observed for the Pd complex-in-a-complex, possibly because the Pd guest is released from the host cage complex more easily than its Pt counterpart.
Therrien, B., Süss-Fink, G., Govindaswamy, P., Renfrew, A. K. & Dyson, P. J. The “complex-in-a-complex” cations [(acac)2M⊂Ru6(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+: A Trojan horse for cancer cells. Angew. Chem. Int. Ed. 10.1002/anie.200800186 (2008).
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Davey, S. Covert complexes. Nature Chem (2008). https://doi.org/10.1038/nchem.5