Open AccessTargeting Tumor‐Associated Exosomes with Integrin‐Binding Peptides
Author(s) -
Carney Randy P.,
Hazari Sidhartha,
Rojalin Tatu,
Knudson Alisha,
Gao Tingjuan,
Tang Yuchen,
Liu Ruiwu,
Viitala Tapani,
Yliperttula Marjo,
Lam Kit S.
Publication year - 2017
Publication title -
advanced biosystems
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.153
H-Index - 18
ISSN - 2366-7478
DOI - 10.1002/adbi.201600038
Subject(s) - microvesicles , flow cytometry , integrin , microbiology and biotechnology , chemistry , proteomics , cancer cell , exosome , biology , microrna , cancer research , cell , cancer , biochemistry , gene , genetics
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.