Dataset Information

Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides.

ABSTRACT: 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 ?3?1 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 ?3?1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.

SUBMITTER: Carney RP

PROVIDER: S-EPMC6001286 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides.

Carney Randy P RP Hazari Sidhartha S Rojalin Tatu T Knudson Alisha A Gao Tingjuan T Tang Yuchen Y Liu Ruiwu R Viitala Tapani T Yliperttula Marjo M Lam Kit S KS

Advanced biosystems 20170403 5

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 ...[more]

PMID: 29911169

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Project description:Rationale: Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. Methods: Herein, by manipulating the exosome membrane, blood exosomes with high abundance and safety are engineered as a versatile combinatorial delivery system, where the doxorubicin (Dox) and cholesterol-modified miRNA21 inhibitor (miR-21i) are co-embedded into the lipid bilayer of exosomes, and the magnetic molecules and endosomolytic peptides L17E are bind to the exosome membrane through ligand-receptor coupling and electrostatic interactions, respectively. Results: It is proved that such engineering strategy not only preserves their intrinsic features, but also readily integrates multiple properties of tumor targeting, efficient transfection and gene/chemo combination therapy into blood exosomes. The lipid bilayer structure of exosomes allows them to co-load Dox and miR-21i with high-payloads. Moreover, profiting from the integration of magnetic molecules and L17E peptides, the engineered exosomes exhibit an enhanced tumor accumulation and an improved endosome escape ability, thereby specifically and efficiently delivering encapsulated cargos to tumor cells. As a result, a remarkable inhibition of tumor growth is observed in the tumor-bearing mice, and without noticeable side effects. Conclusions: This study demonstrates the potential of engineered blood exosomes as feasible co-delivery nanosystem for tumor-targeted and efficient combination therapy. Further development by replacing the drugs combined regimens can potentially make this engineered exosome become a general platform for the design of safe and effective combination therapy modality.

Dataset Information

Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides.

Publications

Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides.

Similar Datasets

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