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

Nanomedicine
Jonas SchnittertJai Prakash

Abstract

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

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Citations

Oct 14, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yating SunChenguang Zhou
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May 5, 2021·Journal of Drug Targeting·Xinru KongGuangxi Zhai

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Methods Mentioned

BETA
transfect
transfection
dynamic light scattering
Fluorescence
FACS
PCR
electrophoresis
flow cytometry

Software Mentioned

Image J

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