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Electrochemotherapy (ECT), as one of the very few available treatments for cutaneous and subcutaneous tumors when surgery and radiotherapy are no longer available, requires applying a proper electric field to the tumor to realize electroporation-mediated cytotoxic drug delivery. It is impossible to exhaust all possible electrical parameters on patients to realize the optimal tradeoff between tumor suppression and adverse effects. To address this issue, this study provides a feasible solution by developing a four-leaf micro-electrode chip (F-MEC) in which the electric field was specially designed by linear distribution to cover all possible electric field strengths for ECT. Methods : We developed a F-MEC that provides a linearly varied electric field and a capacity for in situ observation of cell status. By culturing tumor cells on the F-MEC surface and in situ monitoring the cell responses to ECT drugs, the optimal electric field strength for any given cell type could be rapidly and accurately calculated in a few, or even only one, simple assay. Results : Using this chip, we monitored MCF-7 and A315 cell responses to ECT and determined the optimum ECT voltage. More importantly, we successfully verified that the in vitro determined voltage coincided with the optimal value for in vivo ECT in mice. Conclusion : In this proof-of-concept study, the in vivo tumor suppression assays proved that the optimal parameters acquired from in vitro F-MEC assay could be used for in vivo ECT.

Parametric optimization of electric field strength for cancer electrochemotherapy on a chip-based model