Evaluating polyethyleneimine/DNA nanoparticles-mediated damage to cellular organelles using endoplasmic reticulum stress profile

Dabbaghi, M. and Kazemi Oskuee, R. and Hashemi, K. and Afkhami Goli, A. (2017) Evaluating polyethyleneimine/DNA nanoparticles-mediated damage to cellular organelles using endoplasmic reticulum stress profile. Artificial Cells, Nanomedicine and Biotechnology. pp. 1-8.

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Abstract

Gene therapy has emerged as an influential tool for treating the genetic and specific acquired disorders. Among all kinds of gene delivery systems, the cationic polymer polyethyleneimine (PEI) is considered as a promising non-viral gene delivery vector, although there are still concerns about its magnitude of cytotoxicity. While any cell insult leads to unfolded/misfolded protein accumulation and its consequent unfold protein response, evaluating the expression profile of ER-stress genes would be a sensitive indicator of cell stress. Beside cytotoxicity assays, real-time RT-PCR was used to investigate the effects of PEI nanoparticles on the endoplasmic reticulum. Treating Neuro2A cells revealed that PEI can induce cell toxicity in a concentration-dependent manner. Also, It increased the transcript levels of Grp78 (Bip), Atf4 and Chop, and splicing of Xbp1. To further optimize the transfection properties in Neuro2A cells, PEI was used to deliver a plasmid DNA containing GFP reporter. While different PEI/plasmid ratios revealed similar transfection efficiency, increasing the PEI/plasmid ratio led to induction of ER-stress markers. These results underscored that beside the effectiveness of PEI, using the lowest possible ratio of PEI/plasmid would minimize the detrimental effects of PEI on cells and confer it a beneficial therapeutic importance in nucleic acid delivery. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Item Type: Article
Additional Information: Cited By :5 Export Date: 16 February 2020 Article in Press Correspondence Address: Afkhami Goli, A.Iran; email: a-afkhami@um.ac.ir
Uncontrolled Keywords: Cytotoxicity ER-stress polyethyleneimine unfold protein response Cell membranes Cytology Gene expression Gene therapy Gene transfer Nanoparticles Nucleic acids Polymerase chain reaction Proteins Stress analysis Concentration-dependent manners Endoplasmic reticulum stress ER stress Non-viral gene delivery Nucleic acid deliveries Transfection efficiency Unfold proteins Molecular biology DNA drug carrier heat shock protein molecular chaperone GRP78 nanoparticle X box binding protein 1 XBP1 protein, human animal cell organelle chemistry drug effect gene expression regulation genetic transfection genetics metabolism mouse plasmid tumor cell line Animals Cell Line, Tumor Drug Carriers Heat-Shock Proteins Mice Organelles Plasmids Transfection X-Box Binding Protein 1
Subjects: QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 13 May 2020 07:58
Last Modified: 13 May 2020 07:58
URI: http://eprints.mums.ac.ir/id/eprint/16791

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