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Silica nanostructured platform for affinity capture of tumor-derived exosomes

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Abstract

Early diagnosis of prostate cancer and evaluation of appropriate treatment options requires development of effective and high-throughput selective capture technology for exosomes that are positive for the expression of enzyme-biomarker, prostate-specific membrane antigen (PSMA). Exosomes are small secreted vesicles that play a key role in intercellular communication and cancer progression. PSMA is highly enriched in exosomes excreted by PSMA+ prostate cancer cells. Using PSMA+ cells from the well-established prostate cancer cell line (LNCaP), the secreted exosomes were collected and isolated from the culture medium. The tumor-derived exosomes were selectively captured using a novel silica nanostructure support that had been functionalized with the small-molecule ligand TG97, a known inhibitor of PSMA enzymatic activity that binds irreversibly in the active site of PSMA. The concept was demonstrated using a single cancer type (i.e., prostate cancer), but based on the data obtained the approach may be applicable to a broad panel of biomarker ligands for selective capture of biomarker-positive exosomes from an array of cell types. The approach demonstrated herein overcomes many of the limitations of alternative methods that are often ineffective in isolating tumor-derived exosomes from those derived from normal tissue because of the low yield recovery and the time required for the process. A further advantage is the ability to isolate a specific subpopulation of exosomes relying on the expression of a specific surface marker as well as improved exosome recovery rate.

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Acknowledgements

This work was supported by the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program under Award No. W81XWH-14-1-0449. The authors are grateful for technical assistance from Dr. Christine Davitt and Dr. Valerie Lynch-Holm at the Franceschi Microscopy and Imaging Center and Dr. Amit Bandyopadhyay and Yanning Zhang for assistance with the contact angle study.

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Authors and Affiliations

  1. Materials Science and Engineering Program, Washington State University, Pullman, WA, 99164, USA

    Parissa Ziaei & M. Grant Norton

  2. Department of Chemistry, Washington State University, Pullman, WA, 99164, USA

    Jonathan J. Geruntho & Clifford E. Berkman

  3. School of Mechanical and Materials Engineering, Washington State University, Pullman, WA, 99164, USA

    Oscar G. Marin-Flores & M. Grant Norton

  4. Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA, 99164, USA

    M. Grant Norton

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  1. Parissa Ziaei
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  2. Jonathan J. Geruntho
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  3. Oscar G. Marin-Flores
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  4. Clifford E. Berkman
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  5. M. Grant Norton
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Correspondence to M. Grant Norton.

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Ziaei, P., Geruntho, J.J., Marin-Flores, O.G. et al. Silica nanostructured platform for affinity capture of tumor-derived exosomes. J Mater Sci 52, 6907–6916 (2017). https://doi.org/10.1007/s10853-017-0905-0

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  • DOI: https://doi.org/10.1007/s10853-017-0905-0

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