Institute of Molecular Medicine, Peking University, Beijing 100871, China.
National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing 100871, China.
Theranostics. 2018 Jan 1;8(2):358-368. doi: 10.7150/thno.21099. eCollection 2018.
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. : We developed a F-MEC that provides a linearly varied electric field and a capacity for observation of cell status. By culturing tumor cells on the F-MEC surface and 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. : 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 determined voltage coincided with the optimal value for ECT in mice. : In this proof-of-concept study, the tumor suppression assays proved that the optimal parameters acquired from F-MEC assay could be used for ECT.
电化学疗法 (ECT) 是一种为数不多的适用于手术和放疗无法实施的皮肤和皮下肿瘤的治疗方法，它需要在肿瘤上施加适当的电场，以实现电穿孔介导的细胞毒性药物输送。不可能对患者穷尽所有可能的电参数，以实现肿瘤抑制和不良反应之间的最佳权衡。为了解决这个问题，本研究通过开发四叶微电极芯片 (F-MEC) 提供了一种可行的解决方案，其中电场通过线性分布进行了专门设计，以覆盖 ECT 的所有可能电场强度。我们开发了一种 F-MEC，它提供了线性变化的电场和观察细胞状态的能力。通过在 F-MEC 表面培养肿瘤细胞，并监测细胞对 ECT 药物的反应，我们可以在几次，甚至仅一次简单的测定中，快速准确地计算出任何给定细胞类型的最佳电场强度。使用该芯片，我们监测了 MCF-7 和 A315 细胞对 ECT 的反应，并确定了最佳的 ECT 电压。更重要的是，我们成功地验证了所确定的电压与小鼠 ECT 的最佳值相吻合。在这项概念验证研究中，肿瘤抑制试验证明了从 F-MEC 测定中获得的最佳参数可用于 ECT。
