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

doi:10.2217/nnm-2017-0054

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

Department of Biomaterials, Science & Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente, Enschede, The Netherlands.
Department of Biochemistry, Radboud Institute for Molecular LifeSciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1369-1384
Journal	Nanomedicine
Volume	12
Issue number	12
DOIs	https://doi.org/10.2217/nnm-2017-0054
Publication status	Published - 19 May 2017

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2217/nnm-2017-0054

Anti-MicroRNA Targeting Using Peptide-Based Nanocomplexes to Inhibit Differentiation of Human Pancreatic Stellate CellsFinal published version, 4.14 MBLicence: Taverne

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

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, microRNA-199a, miRNA delivery, nanocomplexes, pancreatic cancer, tumor microenvironment",

author = "Jonas Schnittert and Kuninty, \{Praneeth R.\} and Bystry, \{Tomasz F\} and Roland Brock and Gert Storm and Jai Prakash",

year = "2017",

month = may,

day = "19",

doi = "10.2217/nnm-2017-0054",

language = "English",

volume = "12",

pages = "1369--1384",

journal = "Nanomedicine",

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TY - JOUR

T1 - Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells

AU - Schnittert, Jonas

AU - Kuninty, Praneeth R.

AU - Bystry, Tomasz F

AU - Brock, Roland

AU - Storm, Gert

AU - Prakash, Jai

PY - 2017/5/19

Y1 - 2017/5/19

N2 - 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.

AB - 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.

KW - cancer-associated fibroblasts

KW - cell-penetrating peptides

KW - microRNA-199a

KW - miRNA delivery

KW - nanocomplexes

KW - pancreatic cancer

KW - tumor microenvironment

U2 - 10.2217/nnm-2017-0054

DO - 10.2217/nnm-2017-0054

M3 - Article

C2 - 28524768

SN - 1743-5889

VL - 12

SP - 1369

EP - 1384

JO - Nanomedicine

JF - Nanomedicine

IS - 12

ER -

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

Abstract

Keywords

UN SDGs

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