Organic Electronic Platform for Real-time Phenotypic Screening of Extracellular Vesicle-driven Breast Cancer Metastasis.

Tumour-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in non-malignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious anti-metastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, we report the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, non-invasive monitoring of TEV-induced EMT and screening of anti-metastatic drugs. TEVs derived from the triple-negative breast cancer (TNBC) cell line MDA-MB-231 induced EMT in non-malignant breast epithelial cells (MCF10A) over a 9-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype were obtained using OECTs. Further, we identify heparin, a competitive inhibitor of cell surface receptors, as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of our platform for TEV-targeted drug discovery, allowing for facile modelling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as anti-metastatic drug candidates.