TY - JOUR
T1 - 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
AU - Lum, Tsz Shan
AU - HO, Cheuk Lam
AU - Tsoi, Yeuk Ki
AU - Siu, Chi Ho
AU - YUE, Patrick Y K
AU - WONG, Wai Yeung
AU - LEUNG, Kelvin S Y
N1 - Funding Information:
T.-S. Lum acknowledges the receipt of a postgraduate studentship from the University Grants Council. K.S.-Y. Leung and W.-Y. Wong thank the Partner State Key Laboratory of Environmental and Biological Analysis [project numbers: SKLP-14-15-P006 and SKLP-14-15-P011] for financial support. We also thank the financial support from the National Natural Science Foundation of China (Grant No.: 51373145 ), Hong Kong Research Grants Council (HKBU203312), Hong Kong Baptist University (FRG2/12-13/067 and FRG2/12-13/083) and Areas of Excellence Scheme, University Grants Committee of HKSAR (AoE/P-03/08).
PY - 2016/6/20
Y1 - 2016/6/20
N2 - 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.
AB - 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.
KW - Abbreviations LA-ICP-MS laser ablation-inductively coupled plasma-mass spectrometry
KW - FFPE formalin fixed-paraffin embedding
UR - http://www.scopus.com/inward/record.url?scp=84971328612&partnerID=8YFLogxK
U2 - 10.1016/j.ijms.2016.05.005
DO - 10.1016/j.ijms.2016.05.005
M3 - Journal article
AN - SCOPUS:84971328612
SN - 1387-3806
VL - 404
SP - 40
EP - 47
JO - International Journal of Mass Spectrometry
JF - International Journal of Mass Spectrometry
ER -
