All cells expel a variety of nano-sized 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 we demonstrate
peptide binding to
tumor-associated EVs via overexpressed
membrane protein. We find that SKOV-3 ovarian
tumor cells and their released EVs express α3β1
integrin, which can be targeted by our 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 enabled us to differentiate
cancer-associated exosomes from non-
cancer exosomes. Furthermore, we introduce the foundation for a highly specific detection platform for
tumor-EVs in
solution with biosensor surface-immobilized LXY30. 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.