Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides

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http://hdl.handle.net/10138/298667

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Carney , R P , Hazari , S , Rojalin , T , Knudson , A , Gao , T , Tang , Y , Liu , R , Viitala , T , Yliperttula , M & Lam , K S 2017 , ' Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides ' , Advanced Biosystems , vol. 1 , no. 5 , 1600038 . https://doi.org/10.1002/adbi.201600038

Title: Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides
Author: Carney, Randy P.; Hazari, Sidhartha; Rojalin, Tatu; Knudson, Alisha; Gao, Tingjuan; Tang, Yuchen; Liu, Ruiwu; Viitala, Tapani; Yliperttula, Marjo; Lam, Kit S.
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Drug Research Program
Date: 2017-05
Language: eng
Number of pages: 12
Belongs to series: Advanced Biosystems
ISSN: 2366-7478
URI: http://hdl.handle.net/10138/298667
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 alpha(3)beta(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 alpha(3)beta(1) integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
Subject: biosensors
cancer
diagnostics
exosomes
optical tweezers
SURFACE-PLASMON RESONANCE
EXTRACELLULAR VESICLES
HIGH-AFFINITY
CANCER EXOSOMES
LIBRARY
IDENTIFICATION
ADSORPTION
MICRORNA
RECEPTOR
CELLS
216 Materials engineering
317 Pharmacy
318 Medical biotechnology
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