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Epithelial ovarian cancer affects approximately 240,000 women worldwide with an estimated of 152,000 deaths per year. Common treatments include surgery or chemotherapy using a combination of carboplatin and taxane. Unfortunately, approximately 75% patients relapse within 18 months. Of these relapsed patient, an estimate of 85% experience carboplatin resistance. The effect is devastating. One way to combat this emerging drug resistance problem is the development of novel drugs. However, cellular mechanisms of carboplatin-resistance are poorly understood. Without a thorough understanding of resistance mechanisms, developing long-lasting effective drugs for long term treatment is a challenging problem. Therefore, there is a dire need to develop methods to detect and study resistance mechanisms. One suggested mechanism is the inhibition of drug uptake to prevent the intracellular accumulation of the drug. The presented work describes the quantification of carboplatin uptake in ovarian cancer cells. For this purpose, carboplatin is thoroughly characterized by voltammetry and its suitability for physiological bioelectrochemical studies is assessed. Diffusion and adsorption processes of carboplatin are evaluated, its dependence on pH is investigated, and a limit of detection for carboplatin at unmodified Pt electrodes is identified, without the need of expensive and time-intense electrode modification strategies. The influx and efflux of carboplatin into/from ovarian cancer cells are quantified by electrochemistry to better understand mechanisms of carboplatin chemoresistance. Results emerging from this research will be important for future medical research developing novel agents to combat chemoresistance and will present the basis for future long-term funding applications under this collaboration. Reference: Luu H.T.L., Nachtigal M.W., Kuss S.: Electrochemical Characterization of Carboplatin at Unmodified Platinum Electrodes and its Application to Drug Uptake Studies in Ovarian Cancer Cells. Journal of Electroanalytical Chemistry 2020, 872C, 114253. |
