A Systematic Evaluation of Factors Affecting Extracellular Vesicle Uptake by Breast Cancer Cells

Devin M. Stranford, Michelle E. Hung, Emma S. Gargus, Ramille Nirav Shah, Joshua N Leonard

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Extracellular vesicles (EVs) are nanometer-scale particles that are secreted by cells and mediate intercellular communication by transferring biomolecules between cells. Harnessing this mechanism for therapeutic biomolecule delivery represents a promising frontier for regenerative medicine and other clinical applications. One challenge to realizing this goal is that to date, our understanding of which factors affect EV uptake by recipient cells remains incomplete. In this study, we systematically investigated such delivery questions in the context of breast cancer cells, which are one of the most well-studied cell types with respect to EV delivery and therefore comprise a facile model system for this investigation. By displaying various targeting peptides on the EV surface, we observed that although displaying GE11 on EVs modestly increased uptake by MCF-7 cells, neuropeptide Y (NPY) display had no effect on uptake by the same cells. In contrast, neurotensin (NTS) and urokinase plasminogen activator (uPA) display reduced EV uptake by MDA-MB-231 cells. Interestingly, EV uptake rate did not depend on the source of the EVs; breast cancer cells demonstrated no increase in uptake on administration of breast cancer-derived EVs in comparison to HEK293FT-derived EVs. Moreover, EV uptake was greatly enhanced by delivery in the presence of polybrene and spinoculation, suggesting that maximal EV uptake rates are much greater than those observed under basal conditions in cell culture. By investigating how the cell's environment might provide cues that impact EV uptake, we also observed that culturing cells on soft matrices significantly enhanced EV uptake, compared to culturing on stiff tissue culture polystyrene. Each of these observations provides insights into the factors impacting EV uptake by breast cancer cells, while also providing a basis of comparison for systematically evaluating and perhaps enhancing EV uptake by various cell types.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalTissue Engineering - Part A
Volume23
Issue number21-22
DOIs
StatePublished - Nov 1 2017

Fingerprint

Cells
Biomolecules
Breast Neoplasms
Hexadimethrine Bromide
Display devices
Neurotensin
Tissue culture
Plasminogen Activators
Neuropeptide Y
Polystyrenes
Urokinase-Type Plasminogen Activator
Cell culture
Peptides
Communication
Extracellular Vesicles
Regenerative Medicine
MCF-7 Cells
Cues
Neuropeptides
Cell Culture Techniques

Keywords

  • EVs
  • breast cancer
  • exosomes
  • extracellular vesicles

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Stranford, Devin M. ; Hung, Michelle E. ; Gargus, Emma S. ; Shah, Ramille Nirav ; Leonard, Joshua N. / A Systematic Evaluation of Factors Affecting Extracellular Vesicle Uptake by Breast Cancer Cells. In: Tissue Engineering - Part A. 2017 ; Vol. 23, No. 21-22. pp. 1274-1282.
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A Systematic Evaluation of Factors Affecting Extracellular Vesicle Uptake by Breast Cancer Cells. / Stranford, Devin M.; Hung, Michelle E.; Gargus, Emma S.; Shah, Ramille Nirav; Leonard, Joshua N.

In: Tissue Engineering - Part A, Vol. 23, No. 21-22, 01.11.2017, p. 1274-1282.

Research output: Contribution to journalArticle

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