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Updated: Mar 2, 2026
An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate
Jonas Schnittert1, Praneeth R Kuninty1, Tomasz F Bystry1
1Department of Biomaterials, Science & Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente, Enschede, The Netherlands.
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.
