CHAPTER 15: Platinum
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Published:09 Jul 2014
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F. Arnesano, M. Losacco, and G. Natile, in Binding, Transport and Storage of Metal Ions in Biological Cells, ed. W. Maret and A. Wedd, The Royal Society of Chemistry, 2014, pp. 429-460.
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Platinum (Pt) is not a native metal in biology, but is the key component of selected anti-cancer drugs with universally recognized efficacy. Three Pt(II) compounds (cisplatin, carboplatin and oxaliplatin) are currently used, mainly for the clinical treatment of solid tumours, given favourable ligand-exchange kinetics and ability to interact with DNA, prompting malignant cell killing. Similarly to other chemotherapeutics, also platinum drugs can develop resistance and exhibit adverse side effects depending on their interaction with other cellular targets, in addition to nuclear DNA. A recent advancement in this field is the discovery of molecular mechanisms of transport of platinum drugs, beside passive diffusion. Interestingly, proteins responsible for copper (Cu) homeostasis (namely CTR1 and CTR2, ATOX1, ATP7A and ATP7B) have been found to mobilize also cisplatin and its derivatives. The accumulating bulk of information can significantly contribute to the set-up of new therapeutic protocols and to the rational design of more effective platinum drugs, with improved bioavailability and reduced toxicity. Platinum is also largely used, in combination with other heavy metals, such as palladium, in the fabrication of automobile catalytic converters, with consequent release in the environment. Indeed, Pt exposure may represent a health risk, particularly at the chronic level.