Cell penetrating peptides fail to induce an innate immune response in epithelial cells in vitro

Implications for continued therapeutic use

Edward Carter, Chun Yin Lau, David Tosh, Stephen G. Ward, Randall J. Mrsny

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Cell penetrating peptides (CPPs) offer the exciting potential of effectively delivering macromolecules to the cytoplasm of a cell that are otherwise impermeable to the plasma membrane. Although the use of these peptides has so far been well tolerated in clinical trials, it is important to remember that some of these CPPs were originally derived from pathogenic material. We therefore sought to determine if three of the most widely studied CPPs; HIV-TAT, Antennapedia and Transportan, initiated an immune response in epithelial cells. Using conditions where these peptides efficiently delivered a rhodamine tagged BSA cargo to the interior of epithelial cells, we failed to observe an effect on cell viability as determined by MTT assay (P > 0.05). Further, CPP-mediated delivery of this protein cargo failed to activate NFκB, which would be indicative of toll-like receptor signalling. Finally, no significant increase in the release of the inflammatory cytokines interleukin (IL)-8 and IL-6 was detected in epithelial cells exposed to CPP complexes for 72 h (P > 0.05). Together, these results indicate that these commonly used CPPs are passive carriers that do not initiate epithelial cell-associated ‘danger signals’ during the process of cytoplasmic delivery of a model protein cargo.
Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume85
Issue number1
DOIs
Publication statusPublished - 1 Sep 2013

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Cell-Penetrating Peptides
Therapeutic Uses
Innate Immunity
Epithelial Cells
Peptides
Rhodamines
Toll-Like Receptors
Interleukin-8
In Vitro Techniques
Interleukin-6
Cell Survival
Cytoplasm
Proteins
Cell Membrane
Clinical Trials
HIV
Cytokines

Cite this

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abstract = "Cell penetrating peptides (CPPs) offer the exciting potential of effectively delivering macromolecules to the cytoplasm of a cell that are otherwise impermeable to the plasma membrane. Although the use of these peptides has so far been well tolerated in clinical trials, it is important to remember that some of these CPPs were originally derived from pathogenic material. We therefore sought to determine if three of the most widely studied CPPs; HIV-TAT, Antennapedia and Transportan, initiated an immune response in epithelial cells. Using conditions where these peptides efficiently delivered a rhodamine tagged BSA cargo to the interior of epithelial cells, we failed to observe an effect on cell viability as determined by MTT assay (P > 0.05). Further, CPP-mediated delivery of this protein cargo failed to activate NFκB, which would be indicative of toll-like receptor signalling. Finally, no significant increase in the release of the inflammatory cytokines interleukin (IL)-8 and IL-6 was detected in epithelial cells exposed to CPP complexes for 72 h (P > 0.05). Together, these results indicate that these commonly used CPPs are passive carriers that do not initiate epithelial cell-associated ‘danger signals’ during the process of cytoplasmic delivery of a model protein cargo.",
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AU - Ward, Stephen G.

AU - Mrsny, Randall J.

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