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Nanomedicine (Lond). 2017 May 19. doi: 10.2217/nnm-2017-0054. [Epub ahead of print]

Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells.

Author information

1
Department of Biomaterials, Science & Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente, Enschede, The Netherlands.
2
Department of Biochemistry, Radboud Institute for Molecular LifeSciences, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.

Abstract

AIM:

To develop novel peptide-based nanocomplexes (NCs) for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells (hPSCs), precursors of cancer-associated fibroblasts.

MATERIALS & METHODS:

NCs of anti-miRNA oligonucleotides and cell-penetrating peptides (different variants) were formed and characterized. The effects of anti-miR-199a delivery on hPSC differentiation and 3D heterospheroid formation were investigated.

RESULTS:

Dimeric cell-penetrating peptide based NCs (NC-2) showed 130-fold higher uptake by hPSCs compared with monomer-based NCs (NC-1) and tenfold higher uptake compared with general fibroblasts and different pancreatic tumor cells. Interestingly, delivery of anti-miR-199a inhibited hPSC differentiation into cancer-associated fibroblasts and inhibited the size of 3D heterospheroids comprised of hPSCs and tumor cells.

CONCLUSION:

Our NCs present a highly efficient anti-miRNA delivery system to hPSCs to inhibit their protumorigenic activity.

KEYWORDS:

cancer-associated fibroblasts; cell-penetrating peptides; miRNA delivery; microRNA-199a; nanocomplexes; pancreatic cancer; tumor microenvironment

PMID:
28524768
DOI:
10.2217/nnm-2017-0054

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