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Detection of Breast Cancer-Specific Extracellular Vesicles with Fiber-Optic SPR Biosensor.
Int J Mol Sci. 2023 Feb 13; 24(4)IJ

Abstract

Extracellular vesicles (EVs) have attracted great attention as potential biomarkers for cancer diagnostics. Although several technologies have been developed for EV detection, many of them are still not applicable to clinical settings as they rely on complex EV isolation processes, while lacking sensitivity, specificity or standardization. To solve this problem, we have developed a sensitive breast cancer-specific EV detection bioassay directly in blood plasma using a fiber-optic surface plasmon resonance (FO-SPR) biosensor, previously calibrated with recombinant EVs. First, we established a sandwich bioassay to detect SK-BR-3 EVs by functionalizing the FO-SPR probes with anti-HER2 antibodies. A calibration curve was built using an anti-HER2/Banti-CD9 combination, resulting in an LOD of 2.1 × 107 particles/mL in buffer and 7 × 108 particles/mL in blood plasma. Next, we investigated the potential of the bioassay to detect MCF7 EVs in blood plasma using an anti-EpCAM/Banti-mix combination, obtaining an LOD of 1.1 × 10 8 particles/mL. Finally, the specificity of the bioassay was proven by the absence of signal when testing plasma samples from 10 healthy people unknown to be diagnosed with breast cancer. The remarkable sensitivity and specificity of the developed sandwich bioassay together with the advantages of the standardized FO-SPR biosensor highlight outstanding potential for the future of EV analysis.

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Authors+Show Affiliations

Yildizhan Y
Department of Biosystems, Biosensors Group, Katholieke Universiteit Leuven, 3001 Leuven, Belgium.
Driessens K
Department of Biosystems, Biosensors Group, Katholieke Universiteit Leuven, 3001 Leuven, Belgium.
Tsao HSK
Department of Biosystems, Biosensors Group, Katholieke Universiteit Leuven, 3001 Leuven, Belgium.
Boiy R
Laboratory of Experimental Cancer Research, Cancer Research Institute Ghent, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium.
Thomas D
PharmAbs, The KU Leuven Antibody Center, University of Leuven, 3000 Leuven, Belgium.
Geukens N
PharmAbs, The KU Leuven Antibody Center, University of Leuven, 3000 Leuven, Belgium.
Hendrix A
Laboratory of Experimental Cancer Research, Cancer Research Institute Ghent, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium.
Lammertyn J
Department of Biosystems, Biosensors Group, Katholieke Universiteit Leuven, 3001 Leuven, Belgium.
Spasic D
Department of Biosystems, Biosensors Group, Katholieke Universiteit Leuven, 3001 Leuven, Belgium.

MeSH

FemaleHumansBiomarkersBiosensing TechniquesBreast NeoplasmsExtracellular VesiclesSurface Plasmon Resonance

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36835174

Citation

Yildizhan, Yagmur, et al. "Detection of Breast Cancer-Specific Extracellular Vesicles With Fiber-Optic SPR Biosensor." International Journal of Molecular Sciences, vol. 24, no. 4, 2023.
Yildizhan Y, Driessens K, Tsao HSK, et al. Detection of Breast Cancer-Specific Extracellular Vesicles with Fiber-Optic SPR Biosensor. Int J Mol Sci. 2023;24(4).
Yildizhan, Y., Driessens, K., Tsao, H. S. K., Boiy, R., Thomas, D., Geukens, N., Hendrix, A., Lammertyn, J., & Spasic, D. (2023). Detection of Breast Cancer-Specific Extracellular Vesicles with Fiber-Optic SPR Biosensor. International Journal of Molecular Sciences, 24(4). https://doi.org/10.3390/ijms24043764
Yildizhan Y, et al. Detection of Breast Cancer-Specific Extracellular Vesicles With Fiber-Optic SPR Biosensor. Int J Mol Sci. 2023 Feb 13;24(4) PubMed PMID: 36835174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of Breast Cancer-Specific Extracellular Vesicles with Fiber-Optic SPR Biosensor. AU - Yildizhan,Yagmur, AU - Driessens,Kaat, AU - Tsao,Hong Shen Kevin, AU - Boiy,Robin, AU - Thomas,Debby, AU - Geukens,Nick, AU - Hendrix,An, AU - Lammertyn,Jeroen, AU - Spasic,Dragana, Y1 - 2023/02/13/ PY - 2023/01/14/received PY - 2023/02/02/revised PY - 2023/02/09/accepted PY - 2023/2/25/entrez PY - 2023/2/26/pubmed PY - 2023/3/3/medline KW - EpCAM KW - HER2 KW - biosensors KW - breast cancer KW - extracellular vesicles KW - fiber-optic surface plasmon resonance JF - International journal of molecular sciences JO - Int J Mol Sci VL - 24 IS - 4 N2 - Extracellular vesicles (EVs) have attracted great attention as potential biomarkers for cancer diagnostics. Although several technologies have been developed for EV detection, many of them are still not applicable to clinical settings as they rely on complex EV isolation processes, while lacking sensitivity, specificity or standardization. To solve this problem, we have developed a sensitive breast cancer-specific EV detection bioassay directly in blood plasma using a fiber-optic surface plasmon resonance (FO-SPR) biosensor, previously calibrated with recombinant EVs. First, we established a sandwich bioassay to detect SK-BR-3 EVs by functionalizing the FO-SPR probes with anti-HER2 antibodies. A calibration curve was built using an anti-HER2/Banti-CD9 combination, resulting in an LOD of 2.1 × 107 particles/mL in buffer and 7 × 108 particles/mL in blood plasma. Next, we investigated the potential of the bioassay to detect MCF7 EVs in blood plasma using an anti-EpCAM/Banti-mix combination, obtaining an LOD of 1.1 × 10 8 particles/mL. Finally, the specificity of the bioassay was proven by the absence of signal when testing plasma samples from 10 healthy people unknown to be diagnosed with breast cancer. The remarkable sensitivity and specificity of the developed sandwich bioassay together with the advantages of the standardized FO-SPR biosensor highlight outstanding potential for the future of EV analysis. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/36835174/Detection_of_Breast_Cancer_Specific_Extracellular_Vesicles_with_Fiber_Optic_SPR_Biosensor_ DB - PRIME DP - Unbound Medicine ER -