N‑Cadherin Nanoantagonist Driven Mesenchymal-to-Epithelial Transition in Fibroblasts for Improving Reprogramming Efficiency

Induced pluripotent stem cells (iPSCs) hold promise in revolutionizing medicine; however, their application potential is limited because of low reprogramming efficiency. Mesenchymal-to-epithelial transition (MET) has been proved to involve reprogramming of somatic cells into iPSCs, making it a promi...

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Published in:Nano letters Vol. 21; no. 13; pp. 5540 - 5546
Main Authors: Meng, Xia, Zhou, Anwei, Huang, Yu, Zhang, Yu, Xu, Yurui, Shao, Kaifeng, Ning, Xinghai
Format: Journal Article
Language:English
Published: United States American Chemical Society 14.07.2021
Subjects:
Animals
Cadherins - antagonists & inhibitors
Cadherins - genetics
Cellular Reprogramming
Epithelial-Mesenchymal Transition
Fibroblasts
Gold
Induced Pluripotent Stem Cells
Metal Nanoparticles
Mice
ADH-1 functionalized gold nanoparticles
induced pluripotent stem cells
N-cadherin
reprogramming efficiency
mesenchymal-to-epithelial transition
ISSN:1530-6984, 1530-6992, 1530-6992
Online Access:Get full text
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Summary:Induced pluripotent stem cells (iPSCs) hold promise in revolutionizing medicine; however, their application potential is limited because of low reprogramming efficiency. Mesenchymal-to-epithelial transition (MET) has been proved to involve reprogramming of somatic cells into iPSCs, making it a promising target for enhancing generation of iPSCs. Here, we nanoengineered N-cadherin-blocking peptide ADH-1 with gold nanoparticles, generating a multivalent N-cadherin antagonist (ADH-AuNPs), for improving reprogramming efficiency through driving cell MET. ADH-AuNPs exhibited good biocompatibility and showed higher N-cadherin inhibitory activity than ADH-1 due to multivalency, thereby enhancing cell-state reprogramming toward epithelial lineages. Particularly, ADH-AuNPs improved reprogramming efficiency by more than 7-fold after introduction of four Yamanaka factors. Importantly, ADH-AuNPs generated iPSCs displayed high stemness and pluripotency in vitro and in vivo. Therefore, we provide a cooperative strategy for promoting the iPSC generation efficacy.
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ISSN:1530-6984
1530-6992
1530-6992
DOI:10.1021/acs.nanolett.1c00880