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Schnittert J, Kuninty PR, Bystry TF, et al. Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells. Nanomedicine (Lond). 2017;12(12):1369-1384doi: 10.2217/nnm-2017-0054.
Schnittert, J., Kuninty, P. R., Bystry, T. F., Brock, R., Storm, G., & Prakash, J. (2017). Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells. Nanomedicine (London, England), 12(12), 1369-1384. https://doi.org/10.2217/nnm-2017-0054
Schnittert, Jonas, et al. "Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells." Nanomedicine (London, England) vol. 12,12 (2017): 1369-1384. doi: https://doi.org/10.2217/nnm-2017-0054
Schnittert J, Kuninty PR, Bystry TF, Brock R, Storm G, Prakash J. Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells. Nanomedicine (Lond). 2017 Jun;12(12):1369-1384. doi: 10.2217/nnm-2017-0054. Epub 2017 May 19. PMID: 28524768.
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Nanomedicine (Lond). 2017 Jun;12(12):1369-1384. doi: 10.2217/nnm-2017-0054. Epub 2017 May 19.

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

Nanomedicine (London, England)

Jonas Schnittert, Praneeth R Kuninty, Tomasz F Bystry, Roland Brock, Gert Storm, Jai Prakash

Affiliations

  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.

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

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

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