Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides

Randy Carney, Sidhartha Hazari, Tatu Rojalin, Alisha Knudson, Tingjuan Gao, Yuchen Tang, Ruiwu Liu, Tapani Viitala, Marjo Yliperttula, Kit Lam

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express α 3 β 1 integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to α 3 β 1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.

Original languageEnglish (US)
Article number1600038
JournalAdvanced Biosystems
Volume1
Issue number5
DOIs
StatePublished - May 1 2017

Keywords

  • biosensors
  • cancer
  • diagnostics
  • exosomes
  • optical tweezers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Carney, R., Hazari, S., Rojalin, T., Knudson, A., Gao, T., Tang, Y., Liu, R., Viitala, T., Yliperttula, M., & Lam, K. (2017). Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides. Advanced Biosystems, 1(5), [1600038]. https://doi.org/10.1002/adbi.201600038