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; R. M. Owens

doi:10.1002/adhm.202301194

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, R. M. Owens

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English (US)
Journal	Advanced healthcare materials
DOIs	https://doi.org/10.1002/adhm.202301194
State	Published - May 12 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-05-18
Acknowledged KAUST grant number(s): OSR-2018-CRG7-3709
Acknowledgements: This publication was supported by the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. OSR-2018-CRG7-3709. W.C.T. acknowledges funding from the Cambridge Commonwealth, European & International Trust and Churchill College at Cambridge University. J.U. acknowledges funding from the National Science Foundation GraduateResearch Fellowship [Grant Number DGE-1650441), and the Sloan Foundation (Grant number 70481). R.M. acknowledges funding from EPSRC Cambridge NanoDTC under award EP/S022953/1.S.P. acknowledges funding from Cambridge Commonwealth, European & International Trust and Trinity College at Cambridge University and Sensors CDT from EPSRC funding by the Engineering and Physical Sciences Research Council Centre for Doctoral Training in Sensor Technologies and Applications (EP/L015889/1). The authors gratefully acknowledge the Cambridge Advanced Imaging Centrefor their support & assistance with transmission electron microscope imaging. Fig.1 and Fig. 5awere created with Biorender.com and elements of the former were adapted from “Breast Cancer to Brain Metastasis” (2020).

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering
Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/adhm.202301194

https://repository.kaust.edu.sa/bitstream/10754/691750/1/Adv%20Healthcare%20Materials%20-%202023%20-%20Traberg%20-%20Organic%20Electronic%20Platform%20for%20Real%e2%80%90time%20Phenotypic%20Screening%20of%20Extracellular%20%281%29.pdf

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Traberg, W. C., Uribe, J., Druet, V., Hama, A., Moysidou, C.-M., Huerta, M., McCoy, R., Hayward, D., Savva, A., Genovese, A. M. R., Pavagada, S., Lu, Z., Koklu, A., Pappa, A.-M., Fitzgerald, R., Inal, S., Daniel, S., & Owens, R. M. (2023). Organic Electronic Platform for Real-time Phenotypic Screening of Extracellular Vesicle-driven Breast Cancer Metastasis. Advanced healthcare materials. https://doi.org/10.1002/adhm.202301194

@article{a9fbf366d3534a349a05ac522fe64bfb,

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

abstract = "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.",

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

note = "KAUST Repository Item: Exported on 2023-05-18 Acknowledged KAUST grant number(s): OSR-2018-CRG7-3709 Acknowledgements: This publication was supported by the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. OSR-2018-CRG7-3709. W.C.T. acknowledges funding from the Cambridge Commonwealth, European & International Trust and Churchill College at Cambridge University. J.U. acknowledges funding from the National Science Foundation GraduateResearch Fellowship [Grant Number DGE-1650441), and the Sloan Foundation (Grant number 70481). R.M. acknowledges funding from EPSRC Cambridge NanoDTC under award EP/S022953/1.S.P. acknowledges funding from Cambridge Commonwealth, European & International Trust and Trinity College at Cambridge University and Sensors CDT from EPSRC funding by the Engineering and Physical Sciences Research Council Centre for Doctoral Training in Sensor Technologies and Applications (EP/L015889/1). The authors gratefully acknowledge the Cambridge Advanced Imaging Centrefor their support & assistance with transmission electron microscope imaging. Fig.1 and Fig. 5awere created with Biorender.com and elements of the former were adapted from “Breast Cancer to Brain Metastasis” (2020).",

year = "2023",

month = may,

day = "12",

doi = "10.1002/adhm.202301194",

language = "English (US)",

journal = "Advanced healthcare materials",

issn = "2192-2640",

publisher = "Wiley",

}

Traberg, WC, Uribe, J, Druet, V, Hama, A, Moysidou, C-M, Huerta, M, McCoy, R, Hayward, D, Savva, A, Genovese, AMR, Pavagada, S, Lu, Z, Koklu, A, Pappa, A-M, Fitzgerald, R, Inal, S, Daniel, S & Owens, RM 2023, 'Organic Electronic Platform for Real-time Phenotypic Screening of Extracellular Vesicle-driven Breast Cancer Metastasis.', Advanced healthcare materials. https://doi.org/10.1002/adhm.202301194

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, R. M.

N1 - KAUST Repository Item: Exported on 2023-05-18 Acknowledged KAUST grant number(s): OSR-2018-CRG7-3709 Acknowledgements: This publication was supported by the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. OSR-2018-CRG7-3709. W.C.T. acknowledges funding from the Cambridge Commonwealth, European & International Trust and Churchill College at Cambridge University. J.U. acknowledges funding from the National Science Foundation GraduateResearch Fellowship [Grant Number DGE-1650441), and the Sloan Foundation (Grant number 70481). R.M. acknowledges funding from EPSRC Cambridge NanoDTC under award EP/S022953/1.S.P. acknowledges funding from Cambridge Commonwealth, European & International Trust and Trinity College at Cambridge University and Sensors CDT from EPSRC funding by the Engineering and Physical Sciences Research Council Centre for Doctoral Training in Sensor Technologies and Applications (EP/L015889/1). The authors gratefully acknowledge the Cambridge Advanced Imaging Centrefor their support & assistance with transmission electron microscope imaging. Fig.1 and Fig. 5awere created with Biorender.com and elements of the former were adapted from “Breast Cancer to Brain Metastasis” (2020).

PY - 2023/5/12

Y1 - 2023/5/12

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/691750

UR - https://onlinelibrary.wiley.com/doi/10.1002/adhm.202301194

U2 - 10.1002/adhm.202301194

DO - 10.1002/adhm.202301194

M3 - Article

C2 - 37171457

SN - 2192-2640

JO - Advanced healthcare materials

JF - Advanced healthcare materials

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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