Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

Dinusha N. Udukala, Hongwang Wang, Sebastian O. Wendel, Aruni P. Malalasekera, Thilani N. Samarakoon, Asanka S. Yapa, Gayani Abayaweera, Matthew T. Basel, Pamela Maynez, Raquel Ortega, Yubisela Toledo, Leonie Bossmann, Colette Robinson, Katharine E. Janik, Olga B. Koper, Ping Li, Massoud Motamedi, Daniel A. Higgins, Gary Gadbury, Gaohong ZhuDeryl L. Troyer, Stefan H. Bossmann

    Research output: Contribution to journalArticle

    6 Scopus citations

    Abstract

    Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of proteaseactivity- based liquid biopsies for early cancer diagnosis.

    Original languageEnglish (US)
    Pages (from-to)364-373
    Number of pages10
    JournalBeilstein Journal of Nanotechnology
    Volume7
    Issue number1
    DOIs
    StatePublished - 2016

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    Keywords

    • Biophotonics
    • Breast cancer
    • Iron/iron oxide nanoparticle
    • Liquid biopsy
    • Nanodiagnostics detection
    • Nanomedicine
    • Sub-femtomolar limit of detection

    ASJC Scopus subject areas

    • Materials Science(all)
    • Physics and Astronomy(all)
    • Electrical and Electronic Engineering

    Cite this

    Udukala, D. N., Wang, H., Wendel, S. O., Malalasekera, A. P., Samarakoon, T. N., Yapa, A. S., Abayaweera, G., Basel, M. T., Maynez, P., Ortega, R., Toledo, Y., Bossmann, L., Robinson, C., Janik, K. E., Koper, O. B., Li, P., Motamedi, M., Higgins, D. A., Gadbury, G., ... Bossmann, S. H. (2016). Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. Beilstein Journal of Nanotechnology, 7(1), 364-373. https://doi.org/10.3762/bjnano.7.33