Elemental bioimaging of platinum in mouse tissues by laser ablation-inductively coupled plasma-mass spectrometry for the study of localization behavior of structurally similar complexes

• Biodistribution and relative bioavailability of platinum complexes were studied.
• LA-ICP-MS imaging of mice tissue sections of platinum complexes was performed.
• Differential deposition behaviors of platinum complexes were studied.
• The use of LA-ICP-MS for molecular design in drug development was reported.

In the last decade, the number of applications of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in bioimaging has been increasing. To further extend its capability in drug development, in this study, we used this bioimaging tool to visualize deposition behavior of chemically different metallo-complexes, including two that differed only subtly in structure. A systematic approach with in vitro study and ICP-MS elemental analysis were included to supplement the findings.Two chemically distinct platinum complexes (Pt-1 and Pt-2) were synthesized; their potencies were investigated first on different healthy and cancer cell lines and then on mice. The commercialized anti-cancer drug, cis-platin was used as a reference. In animal studies, the mice were given 4 mg/kg of the complex via intraperitoneal injection and sacrificed 24 h post-injection. ICP-MS analysis was performed on six organs to study the bioavailability of the complexes. Pt accumulated in the organs, from greatest to least, from liver > kidney > lung > testis > heart > brain. Among the complexes, the bioavailability showed a general trend of Pt–2 > cis-platin > Pt-1.In LA-ICP-MS bioimaging analysis of paraffin-embedded mouse liver and kidney sections, a spatial resolution of 50 μm was adopted. Deposition trends matched the findings obtained in elemental analysis. In addition, differential deposition of Pt was observed in the kidney sections of mice treated with different complexes. The LA biomaps successfully distinguished the differential distribution of two structurally similar platinum complexes (Pt-1 and Pt-2) in mice liver and kidney. This information is of particular interest because these two Pt-based complexes can potentially be developed into anti-cancer drugs. This work demonstrates that LA-ICP-MS imaging is a valuable tool for therapeutic drug development, especially in assisting molecular modification of metal-containing complexes.

Figure optionsDownload high-quality image (253 K)Download as PowerPoint slide