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.
Fig: Integration of flexible electronics onto a vascularized 3D tumor model: a Flexible interdigitated electrodes and the scheme of the tip. b Steps of the development of the in ovo model of glioblastoma. c Spheroid of U87 cells obtained by 3D cell culture observed under the microscope. d Shell-less culture of a quail embryo with a zoom on the grafted spheroid. e–g pictures of vascularized spheroids observed by fluorescence microscopy. On e and f, vasculature was visualized by injecting Texas Red dextran into the circulation. On (g) in addition to the intravascular injection of Texas Red dextran in the circulatory system (red), spheroid was labeled intravitally with a viability marker (green). h Flexible interdigitated electrodes placed on the in ovo model of glioblastoma, observed by fluorescence microscopy with the same markers than (g). Scale bars: a 2 mm, c 100 µm, d left: 1 cm, right: 200 µm, e–h 400 µm.
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.
Lefevre, M.C., Dijk, G., Kaszas, A. et al. Integrating flexible electronics for pulsed electric field delivery in a vascularized 3D glioblastoma model. npj Flex Electron 5, 19 (2021). https://doi.org/10.1038/s41528-021-00115-x