Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis

Walther C. Traberg, Johana Uribe, Victor Druet, Adel Hama, Chrysanthi Maria Moysidou, Miriam Huerta, Reece McCoy, Daniel Hayward, Achilleas Savva, Amaury M.R. Genovese, Suraj Pavagada, Zixuan Lu, Anil Koklu, Anna Maria Pappa, Rebecca Fitzgerald, Sahika Inal, Susan Daniel, Róisín M. Owens

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-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 are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.

    Original languageBritish English
    Article number2301194
    JournalAdvanced Healthcare Materials
    Volume12
    Issue number27
    DOIs
    StatePublished - 27 Oct 2023

    Keywords

    • breast cancer metastasis
    • drug screening
    • exosomes
    • extracellular vesicles
    • organic electronics

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