文献作者：Jonas Schnittert, Praneeth R Kuninty, Tomasz F Bystry, Roland Brock, Gert Storm & Jai Prakash 《Future Medicine》
ABSTRACTS
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.
GRAPHICAL ABSTRACT
In this study, we developed novel cell-penetrating peptide based nanocomplexes (～40 nm) to efficiently deliver anti-miRNA-199a to primary human pancreatic stellate cells (hPSCs). Our nanocomplexes significantly inhibited the differentiation of hPSCs into tumor-promoting human pancreatic tumor stromal myofibroblasts and reduced the growth of in vitro tumor heterospheroids composed of hPSCs and Panc-1 epithelial cancer cells.
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SCREENSHOT
RELATED PRODUCTS
The monomeric form of CPP (VSRRRRRRGGRRRR) and dimeric CPP (RRRRGGRRRRRRSV-CSSC-VSRRRRRRGGRRRR) were custom-synthesized from ChinaPeptides (Shanghai, China).
CHAINING
https://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0054
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