Targeted delivery of a plant-derived monoclonal antibody using pulsed electric fields in a 3D glioblastoma model

Electroporation is a promising technique for enhancing the delivery of therapeutic agents by transiently increasing cell membrane permeability through high-amplitude (from hundreds of V/cm to tens of kV/cm), ultra-short pulsed electric fields (from ms to ns). This technique has shown potential not only for nucleic acid and small molecule delivery but also for the efficient modulation of tumor targets. In this study, we explore, for the first time, the combination of electroporation with an engineered monoclonal antibody targeting tenascin-C, a molecular hallmark of glioblastoma. Using a three-dimensional spheroid model of glioblastoma, we demonstrate that electroporation can enhance antibody binding to tenascin-C in the extracellular matrix, overcoming the structural barriers of the tumor microenvironment. Our results show that electroporation increases antibody access to tumor cells without significant cytotoxicity, highlighting its role as a potentiating tool for antibody-based therapies. Additionally, we utilize plant molecular farming to produce biologically active antibodies, offering a scalable and sustainable platform for large-scale production. This study provides a novel strategy for therapeutic delivery in solid tumors, such as glioblastoma, and offers novel possibilities for other types of cancer.