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Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®

MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson’s disease (PD). Controlling the level of specific miRNAs in the b...

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Main Authors: Almeida, Simoneide Souza Titze de, Horst, Camila Hillesheim, Sánchez, Cristina Soto, Fernandez, Eduardo, Almeida, Ricardo Titze de
Format: Artigo
Language: Inglês
Published: MDPI 2020
Subjects:
MicroRNA
Nanopartículas
Neuromag®
Online Access: https://repositorio.unb.br/handle/10482/39653
https://doi.org/10.3390/molecules23071825
https://orcid.org/0000-0001-7286-1676
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spelling ir-10482-396532020-11-24T10:53:38Z Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag® Almeida, Simoneide Souza Titze de Horst, Camila Hillesheim Sánchez, Cristina Soto Fernandez, Eduardo Almeida, Ricardo Titze de MicroRNA Nanopartículas Neuromag® MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson’s disease (PD). Controlling the level of specific miRNAs in the brain is thus a promising therapeutic strategy for neuroprotection. A fundamental need for miRNA regulation (either replacing or inhibition) is a carrier capable of delivering oligonucleotides into brain cells. This study aimed to examine a polymeric magnetic particle, Neuromag®, for delivery of synthetic miRNA inhibitors in the rat central nervous system. We injected the miRNA inhibitor complexed with Neuromag® into the lateral ventricles next to the striatum, by stereotaxic surgery. Neuromag efficiently delivered oligonucleotides in the striatum and septum areas, as shown by microscopy imaging of fluorescein isothiocyanate (FITC)-labeled oligos in astrocytes and neurons. Transfected oligos showed efficacy concerning miRNA inhibition. Neuromag®-structured miR-134 antimiR (0.36 nmol) caused a significant 0.35 fold decrease of striatal miR-134, as revealed by real-time quantitative polymerase chain reaction (RT-qPCR). In conclusion, the polymeric magnetic particle Neuromag® efficiently delivered functional miRNA inhibitors in brain regions surrounding lateral ventricles, particularly the striatum. This delivery system holds potential as a promising miRNA-based disease-modifying drug and merits further pre-clinical studies using animal models of PD. 2020-11-24T10:53:38Z 2020-11-24T10:53:38Z 2018-07-23 Artigo ALMEIDA, Simoneide Souza Titze de et al. Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®. Molecules, v. 23, n. 7, 1825, 2018. DOI: https://doi.org/10.3390/molecules23071825. Disponível em: https://www.mdpi.com/1420-3049/23/7/1825. Acesso em: 24 nov. 2020. https://repositorio.unb.br/handle/10482/39653 https://doi.org/10.3390/molecules23071825 https://orcid.org/0000-0001-7286-1676 Inglês Acesso Aberto © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf MDPI
institution REPOSITORIO UNB
collection REPOSITORIO UNB
language Inglês
topic MicroRNA
Nanopartículas
Neuromag®
spellingShingle MicroRNA
Nanopartículas
Neuromag®
Almeida, Simoneide Souza Titze de
Horst, Camila Hillesheim
Sánchez, Cristina Soto
Fernandez, Eduardo
Almeida, Ricardo Titze de
Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
description MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson’s disease (PD). Controlling the level of specific miRNAs in the brain is thus a promising therapeutic strategy for neuroprotection. A fundamental need for miRNA regulation (either replacing or inhibition) is a carrier capable of delivering oligonucleotides into brain cells. This study aimed to examine a polymeric magnetic particle, Neuromag®, for delivery of synthetic miRNA inhibitors in the rat central nervous system. We injected the miRNA inhibitor complexed with Neuromag® into the lateral ventricles next to the striatum, by stereotaxic surgery. Neuromag efficiently delivered oligonucleotides in the striatum and septum areas, as shown by microscopy imaging of fluorescein isothiocyanate (FITC)-labeled oligos in astrocytes and neurons. Transfected oligos showed efficacy concerning miRNA inhibition. Neuromag®-structured miR-134 antimiR (0.36 nmol) caused a significant 0.35 fold decrease of striatal miR-134, as revealed by real-time quantitative polymerase chain reaction (RT-qPCR). In conclusion, the polymeric magnetic particle Neuromag® efficiently delivered functional miRNA inhibitors in brain regions surrounding lateral ventricles, particularly the striatum. This delivery system holds potential as a promising miRNA-based disease-modifying drug and merits further pre-clinical studies using animal models of PD.
format Artigo
author Almeida, Simoneide Souza Titze de
Horst, Camila Hillesheim
Sánchez, Cristina Soto
Fernandez, Eduardo
Almeida, Ricardo Titze de
author_sort Almeida, Simoneide Souza Titze de
title Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
title_short Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
title_full Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
title_fullStr Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
title_full_unstemmed Delivery of miRNA-targeted oligonucleotides in the rat striatum by magnetofection with Neuromag®
title_sort delivery of mirna-targeted oligonucleotides in the rat striatum by magnetofection with neuromag®
publisher MDPI
publishDate 2020
url https://repositorio.unb.br/handle/10482/39653
https://doi.org/10.3390/molecules23071825
https://orcid.org/0000-0001-7286-1676
_version_ 1684523569774592000
score 13.657419

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