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Single-Cell Analysis of Metallodrugs
Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest.
2. Determination of Intracellular cisPt in Wild Type (wt) and Resitant Cells Using SC-ICP-MS
3. Intracellular cisPt Concentration in A24 and A24dPt8 Cells
4. Difference in cisPt Uptake between wt and Resistant Cells
5. Difference in nuclear cisPt Uptake between wt and Resistant Cells
Average concentration of cisPt in nuclei of sensitive and resistant cells were determined, using measured nuclear volumes. The average cisPt concentration detected by SC-ICP-MS for 8 h in A24 cells was 0.6 ± 0.08 µM cisPt per nucleus, and 1.02 ± 0.27 µM cisPt per nucleus after 16 hours of incubation. In contrast, determination of nuclear cisPt concentration in resistant A24dPt8 cells revealed an average concentration of 0.23 ± 0.06 µM cisPt per nucleus at 8 h. At 16 h, an average of 0.59 ± 0.17 µM cisPt per nucleus was detected. CisPt concentrations measured in nuclei or cells within the same cell line are significantly higher in nuclei than in cells. From SC-ICP-MS measurements, an approximate 2-fold higher concentration of cisPt was found in nuclei compared to A24 cells at 8 h and 16 h, respectively (Fig. 7).
Figure 7. Nuclear and cellular cisPt concentration after incubation of A24 and A24DPt8 cells for ▐ 0h ▐ 8h ▐ 16 hours with 30 µM cisPt.
By SC ICP-MS quantification, it was shown that uptake of cisPt by A24 wt cells is higher than the one of A24dPt8 cisPt resistant cells. Nuclear cisPt concentration is higher than cellular cisPt is both WT and resistant cell lines.
The entry is from 10.3390/ijms22179468
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