TY - JOUR
T1 - Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis
AU - Traberg, Walther C.
AU - Uribe, Johana
AU - Druet, Victor
AU - Hama, Adel
AU - Moysidou, Chrysanthi Maria
AU - Huerta, Miriam
AU - McCoy, Reece
AU - Hayward, Daniel
AU - Savva, Achilleas
AU - Genovese, Amaury M.R.
AU - Pavagada, Suraj
AU - Lu, Zixuan
AU - Koklu, Anil
AU - Pappa, Anna Maria
AU - Fitzgerald, Rebecca
AU - Inal, Sahika
AU - Daniel, Susan
AU - Owens, Róisín M.
N1 - Publisher Copyright:
© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2023/10/27
Y1 - 2023/10/27
N2 - 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.
AB - 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.
KW - breast cancer metastasis
KW - drug screening
KW - exosomes
KW - extracellular vesicles
KW - organic electronics
UR - http://www.scopus.com/inward/record.url?scp=85159812743&partnerID=8YFLogxK
U2 - 10.1002/adhm.202301194
DO - 10.1002/adhm.202301194
M3 - Article
C2 - 37171457
AN - SCOPUS:85159812743
SN - 2192-2640
VL - 12
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 27
M1 - 2301194
ER -