NanoSIMS multi-element imaging reveals internalisation and nucleolar targeting for a highly-charged polynuclear platinum compound

Abstract

Simultaneous multi-element imaging using NanoSIMS (nano-scale secondary ion mass spectrometry), exploiting the novel combination of (195)Pt and (15)N in platinum-am(m)ine antitumour drugs, provides information on the internalisation and subcellular localisation of both metal and ligands, and allows identification of ligand exchange.

Fig. 1

Secondary ion maps acquired by NanoSIMS of fixed sections of an MCF7 cell treated with TriplatinNC (20 μM, 1 h). The ¹⁹⁵Pt⁻ (red) and + ³¹P⁻ (greyscale) overlay shows no colocalisation of Pt and nucleic acids; the overlay of the ¹⁹⁵Pt⁻ (blue) ¹²C¹⁵N⁻ (red) secondary ion maps shows Pt and ¹⁵N are mostly colocalised; the HSI representation of the ¹²C¹⁵N⁻/¹²C¹⁴N⁻ ratio shows enrichment of ¹⁵N in the cytoplasm as well as ‘hotspots’; scale bars = 5 μm.

Fig. 2

Secondary ion maps acquired by NanoSIMS of fixed sections of an MCF7 cell treated with TriplatinNC (20 μM, 2 h). The ¹⁹⁵Pt⁻ secondary ion map and the hue-saturation-intensity (HSI) representation of the ¹²C¹⁵N⁻/¹²C¹⁴N⁻ ratio map, clearly show localisation of both ¹⁹⁵Pt and ¹⁵N within the nucleolus (grey arrow); the overlay of the ¹⁹⁵Pt⁻ (blue) ¹²C¹⁵N⁻ (red) secondary ion maps shows Pt and ¹⁵N are colocalised in some but not all instances; scale bars = 5 μm.

Chart 1

Structures of platinum antitumour compounds. Fully ¹⁵N-labelled cisplatin and TriplatinNC were used in this study.