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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1369-1384
Number of pages16
JournalNanomedicine
Volume12
Issue number12
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

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

Fingerprint Dive into the research topics of 'Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells'. Together they form a unique fingerprint.

  • Cite this