The fate of platinum(II) and platinum(IV) anti-cancer agents in cancer cells and tumours

摘要

SRIXE mapping has been used to gain insight into the fate of platinum(II) and platinum(IV) complexes in cells and tumours treated with anticancer active complexes to facilitate the development of improved drugs. SRIXE maps were collected of thin sections of human ovarian (A2780) cancer cells treated with bromine containing platinum complexes, cis-[PtCl2(3-Brpyr)(NH3)] (3-Brpyr = 3-bromopyridine) and cis, trans, cis-[PtCl2(OAcBr)2(NH3)(2)] (OAcBr = bromoacetate), or a platinum complex with an intercalator attached cis-[PtCl2(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH3)]. After 24 h the complexes appear to be localised in the cell nucleus with a lower concentration in the surrounding cytoplasm. In cells treated with cis[PtCl2(3-Brpyr)(NH3)] the concentration of bromine was substantially higher than in control cells and the bromine was co-localised with the platinum consistent with the 3-bromopyridine ligand remaining bound to the platinum. The cells treated with cis, trans, cis[PtCl2(OAcBr)(2)(NH3)(2)] also showed an increased level of bromine, but to a much lesser extent than for those treated with cis-[PtCl2(3-Brpyr)(NH3)] suggestive of substantial reduction of the platinum(IV) complex. Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour xenograft removed from a mouse 3 h after treatment with cis, trans, cis-[PtCl2(OH)(2)(NH3)(2)] and revealed selective uptake of platinum by one cell. (c) 2006 Elsevier Inc. All rights reserved.