Glioblastoma is a highly aggressive brain tumor, very invasive and thus difficult to eradicate with standard oncology therapies. Bioelectric treatments based on pulsed electric fields have proven to be a successful method to treat cancerous tissues. However, they rely on stiff electrodes, which cause acute and chronic injuries, especially in soft tissues like the brain. Here we demonstrate the feasibility of delivering pulsed electric fields with flexible electronics using an in ovo vascularized tumor model. We show with fluorescence widefield and multiphoton microscopy that pulsed electric fields induce vasoconstriction of blood vessels and evoke calcium signals in vascularized glioblastoma spheroids stably expressing a genetically encoded fluorescence reporter. Simulations of the electric field delivery are compared with the measured influence of electric field effects on cell membrane integrity in exposed tumor cells. Our results confirm the feasibility of flexible electronics as a means of delivering intense pulsed electric fields to tumors in an intravital 3D vascularized model of human glioblastoma.

胶质母细胞瘤是一种侵袭性很强的脑肿瘤，侵袭性很强，因此很难用标准的肿瘤学疗法根除。基于脉冲电场的生物电治疗已被证明是治疗癌组织的成功方法。然而，它们依赖于坚硬的电极，这会导致急性和慢性损伤，特别是在大脑等软组织中。在这里，我们展示了使用卵内血管化肿瘤模型通过柔性电子设备传递脉冲电场的可行性。我们用荧光宽场和多光子显微镜显示脉冲电场诱导血管收缩并在稳定表达基因编码荧光报告基因的血管化胶质母细胞瘤球体中诱发钙信号。将电场传递的模拟与电场效应对暴露的肿瘤细胞中细胞膜完整性的测量影响进行比较。我们的结果证实了柔性电子设备作为一种向人类胶质母细胞瘤活体 3D 血管化模型中的肿瘤提供强脉冲电场的手段的可行性。