A novel microscale platform for leukemia tumor treating field therapy and electrochemical screening

Abstract

Currently, chemotherapy methods are among the most commonly used strategies for all cancer treatments, including leukemia. Despite the marked successes of such therapies, their inevitable side-effects and dose-limiting complications hinder reaching the maximum efficacy. Recently, Tumor Treating Fields (TTFields) that exploits low intensity and intermediate frequency electric fields has shown great promise as a noninvasive cancer therapy. Combining TTFields and conventional chemotherapies allows treatment with lower drug doses, resulting in significant clinical outcomes and fewer side effects. Although such combinational therapies have been used to treat a wide range of cancer types, their potential applications on leukemia have yet to be explored. This study investigates the effects of TTFields on the leukemia cells in combination with imatinib using a novel microelectrode array platform enabling the on-chip application of TTFields. Microfabrication allows applying TTFields by conventional signal generators with a maximum 20 V peak-to-peak external voltage eliminating commonly used high voltage amplifiers. We evaluated the effectiveness of our method with several biological assays, including flow cytometry, Annexin-V staining, and MTT. Our results indicate that combining TTFields and imatinib can halve the required drug dose (1 μM to 0.5 μM) to reach the apoptotic rate (68.55%±2.4%) obtained by imatinib alone. By comparing the cells numbers, after 72 h, the K562 cells number in our combinational treatment were 7% lower than the initial values seeded, suggesting a considerable net reduction in the tumor cell. Furthermore, to explore the underlying mechanism, an electrochemical approach is employed to measure the secreting contents of the leukemia cells after treatment. We concluded that the enhancement in treatment efficacy could be attributed to the induction of intracellular reactive oxygen species by TTFields, resulting in increased cell apoptosis. Our method provides an in vitro basis to assess the application of TTFields in combination with chemotherapy for leukemia cells.