Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides

Publication year: 2017
Authors: Carney R.P. 1, Hazari S. 1, Rojalin T. 2,3, Knudson A. 1, Gao T. 3,4, Tang Y. 3,4, Liu R. 1, Viitala T. 5, Yliperttula M. 5,6, Lam K.S. 1,7
Affiliations:

1 - Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA
2 - Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Helsinki, Finland
3 - Center for Biophotonics, University of California Davis, Sacramento, CA, USA
4 - College of Chemistry, Central China Normal University, Wuhan, China
5 - Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Helsinki, Finland
6 - Department of Pharmaceutical Sciences, University of Padova, Padua, Italy
7 - University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA

Published in: Advanced Biosystems, 2017, Vol. 1 (5), p. 1600038
doi: 10.1002/adbi.201600038

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 α3β1integrin, 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 α3β1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.


MP-SPR keywords: affinity, association and dissociation rate constants, cancer, diagnostics, EVs binding to peptides, exosomes, exosomes from SKOV-3 ovarian tumor cells, extracellular vesicles (EVs), integrin (glycoprotein), interaction kinetics, refractive index, streptavidin – biotin binding, surface bound peptides, thickness