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

Autor: Traberg WC; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Uribe J; Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Olin Hall, Ithaca, NY, 14853, USA., Druet V; Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 3955, Kingdom of Saudi Arabia., Hama A; Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 3955, Kingdom of Saudi Arabia., Moysidou CM; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Huerta M; Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Olin Hall, Ithaca, NY, 14853, USA., McCoy R; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Hayward D; Early Cancer Institute, University of Cambridge, Hutchison Research Centre, Cambridge, CB2 0XZ, UK., Savva A; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Genovese AMR; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Pavagada S; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK.; Early Cancer Institute, University of Cambridge, Hutchison Research Centre, Cambridge, CB2 0XZ, UK., Lu Z; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK., Koklu A; Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 3955, Kingdom of Saudi Arabia., Pappa AM; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK.; Healthcare Innovation Engineering Center, Khalifa University, Abu Dhabi, PO Box 127788, United Arab Emirates.; Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, PO Box 127788, United Arab Emirates., Fitzgerald R; Early Cancer Institute, University of Cambridge, Hutchison Research Centre, Cambridge, CB2 0XZ, UK., Inal S; Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 3955, Kingdom of Saudi Arabia., Daniel S; Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Olin Hall, Ithaca, NY, 14853, USA., Owens RM; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Oct; Vol. 12 (27), pp. e2301194. Date of Electronic Publication: 2023 May 21.
DOI: 10.1002/adhm.202301194
Abstrakt: 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.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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