Reversal of tumor malignization and modulation of cell behaviors through genome editing mediated by a multi-functional nanovector

To effectively reverse tumor malignization by genome editing, a multi-functional self-assembled nanovector for the delivery of a genome editing plasmid specifically to tumor cells was developed. The nanovector core consisting of protamine and calcium carbonate entrapping the CRISPR-Cas9 plasmid is d...

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Veröffentlicht in:Nanoscale 2018-12, Vol.1 (45), p.2129-21218
Hauptverfasser: Liu, Bo-Ya, He, Xiao-Yan, Zhuo, Ren-Xi, Cheng, Si-Xue
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container_title Nanoscale
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creator Liu, Bo-Ya
He, Xiao-Yan
Zhuo, Ren-Xi
Cheng, Si-Xue
description To effectively reverse tumor malignization by genome editing, a multi-functional self-assembled nanovector for the delivery of a genome editing plasmid specifically to tumor cells was developed. The nanovector core consisting of protamine and calcium carbonate entrapping the CRISPR-Cas9 plasmid is decorated by aptamer incorporated heparin. Owing to a high affinity between a MUC1 specific aptamer and mucin 1 (MUC1) overexpressed in tumor cells as well as the interaction between AS1411 and nucleolin on the tumor cell surface and cell nuclei, the nanovector can target the nuclei of tumorous cells for the knockout of focal adhesion kinase (FAK). Notably, the genome editing mediated by our delivery systems can effectively modulate cell behaviors and thus reverse tumor malignization. Up-regulated p53, p16, p21, E-cadherin, CD80, MICA, MICB and Fas, together with down-regulated MMP-9, vimentin, VEGF, TGF-β, CD47 and CD133 in genome edited cells indicate that the genome editing system can inhibit cancerous cell growth, prevent tumor invasion and metastasis, reverse tumor-induced immune suppression, and inhibit cancer stemness. More importantly, the edited cells can maintain the modulated cellular function after succeeding subcultures. A multi-functional nanovector was developed to deliver genome editing plasmids for modulation of cell behaviors and reversal of tumor malignization.
doi_str_mv 10.1039/c8nr07321j
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The nanovector core consisting of protamine and calcium carbonate entrapping the CRISPR-Cas9 plasmid is decorated by aptamer incorporated heparin. Owing to a high affinity between a MUC1 specific aptamer and mucin 1 (MUC1) overexpressed in tumor cells as well as the interaction between AS1411 and nucleolin on the tumor cell surface and cell nuclei, the nanovector can target the nuclei of tumorous cells for the knockout of focal adhesion kinase (FAK). Notably, the genome editing mediated by our delivery systems can effectively modulate cell behaviors and thus reverse tumor malignization. Up-regulated p53, p16, p21, E-cadherin, CD80, MICA, MICB and Fas, together with down-regulated MMP-9, vimentin, VEGF, TGF-β, CD47 and CD133 in genome edited cells indicate that the genome editing system can inhibit cancerous cell growth, prevent tumor invasion and metastasis, reverse tumor-induced immune suppression, and inhibit cancer stemness. 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source MEDLINE; Royal Society Of Chemistry Journals 2008-
subjects Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - metabolism
Calcium carbonate
Cell Movement
Cell Survival
CRISPR-Cas Systems - genetics
Drug Carriers - chemistry
Editing
Focal Adhesion Protein-Tyrosine Kinases - deficiency
Focal Adhesion Protein-Tyrosine Kinases - genetics
Gene Editing - methods
Genomes
HEK293 Cells
HeLa Cells
Humans
Microscopy, Confocal
Mucin-1 - genetics
Mucin-1 - metabolism
Nanoparticles - chemistry
Nuclei (cytology)
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
Plasmids - chemistry
Plasmids - metabolism
Self-assembly
System effectiveness
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumors
title Reversal of tumor malignization and modulation of cell behaviors through genome editing mediated by a multi-functional nanovector
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