Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems

Anna-Laurence Schachner-Nedherer,1 Oliver Werzer,1 Karin Kornmueller,2 Ruth Prassl,2 Andreas Zimmer1 1Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, Graz 8010, Austria; 2Gottfried Schatz Research Center for Cell Signaling, Metabolis...

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Autores principales:	Schachner-Nedherer AL, Werzer O, Kornmueller K, Prassl R, Zimmer A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	drug delivery system (DDS) miRNA-27a amphipathic peptides anti-adipogenic effect 3T3-L1 cells Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/267a761fabaa4d5dac1fc4e29aff261b
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spelling	oai:doaj.org-article:267a761fabaa4d5dac1fc4e29aff261b2021-12-02T08:02:43ZBiological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems1178-2013https://doaj.org/article/267a761fabaa4d5dac1fc4e29aff261b2019-09-01T00:00:00Zhttps://www.dovepress.com/biological-activity-of-mirna-27a-using-peptide-based-drug-delivery-sys-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Anna-Laurence Schachner-Nedherer,1 Oliver Werzer,1 Karin Kornmueller,2 Ruth Prassl,2 Andreas Zimmer1 1Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, Graz 8010, Austria; 2Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Graz 8010, AustriaCorrespondence: Andreas ZimmerInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Graz 8010, AustriaEmail andreas.zimmer@uni-graz.atBackground: Endogenously expressed microRNAs (miRNAs) have attracted attention as important regulators in post-transcriptionally controlling gene expression of various physiological processes. As miRNA dysregulation is often associated with various disease patterns, such as obesity, miRNA-27a might therefore be a promising candidate for miRNA mimic replacement therapy by inhibiting adipogenic marker genes. However, application of naked nucleic acids faces some limitations concerning poor enzymatic stability, bio-membrane permeation and cellular uptake. To overcome these obstacles, the development of appropriate drug delivery systems (DDS) for miRNAs is of paramount importance.Methods: In this work, a triple combination of atomic force microscopy (AFM), brightfield (BF) and fluorescence microscopy was used to trace the cellular adhesion of N-TER peptide-nucleic acid complexes followed by time-dependent uptake studies using confocal laser scanning microscopy (cLSM). To reveal the biological effect of miRNA-27a on adipocyte development after transfection treatment, Oil-Red-O (ORO)- staining was performed to estimate the degree of in lipid droplets accumulated ORO in mature adipocytes by using light microscopy images as well as absorbance measurements.Results: The present findings demonstrated that amphipathic N-TER peptides represent a suitable DDS for miRNAs by promoting non-covalent complexation through electrostatic interactions between both components as well as cellular adhesion of the N-TER peptide – nucleic acid complexes followed by uptake across cell membranes and intracellular release of miRNAs. The anti-adipogenic effect of miRNA-27a in 3T3-L1 cells could be detected in mature adipocytes by reduced lipid droplet formation.Conclusion: The present DDS assembled from amphipathic N-TER peptides and miRNAs is capable of inducing the anti-adipogenic effect of miRNA-27a by reducing lipid droplet accumulation in mature adipocytes. With respect to miRNA mimic replacement therapies, this approach might provide new therapeutic strategies to prevent or treat obesity and obesity-related disorders.Keywords: drug delivery system, DDS, miRNA-27a, amphipathic peptides, anti-adipogenic effect, 3T3-L1 cellsSchachner-Nedherer ALWerzer OKornmueller KPrassl RZimmer ADove Medical Pressarticledrug delivery system (DDS)miRNA-27aamphipathic peptidesanti-adipogenic effect3T3-L1 cellsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 7795-7808 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug delivery system (DDS) miRNA-27a amphipathic peptides anti-adipogenic effect 3T3-L1 cells Medicine (General) R5-920
spellingShingle	drug delivery system (DDS) miRNA-27a amphipathic peptides anti-adipogenic effect 3T3-L1 cells Medicine (General) R5-920 Schachner-Nedherer AL Werzer O Kornmueller K Prassl R Zimmer A Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
description	Anna-Laurence Schachner-Nedherer,1 Oliver Werzer,1 Karin Kornmueller,2 Ruth Prassl,2 Andreas Zimmer1 1Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, Graz 8010, Austria; 2Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Graz 8010, AustriaCorrespondence: Andreas ZimmerInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Graz 8010, AustriaEmail andreas.zimmer@uni-graz.atBackground: Endogenously expressed microRNAs (miRNAs) have attracted attention as important regulators in post-transcriptionally controlling gene expression of various physiological processes. As miRNA dysregulation is often associated with various disease patterns, such as obesity, miRNA-27a might therefore be a promising candidate for miRNA mimic replacement therapy by inhibiting adipogenic marker genes. However, application of naked nucleic acids faces some limitations concerning poor enzymatic stability, bio-membrane permeation and cellular uptake. To overcome these obstacles, the development of appropriate drug delivery systems (DDS) for miRNAs is of paramount importance.Methods: In this work, a triple combination of atomic force microscopy (AFM), brightfield (BF) and fluorescence microscopy was used to trace the cellular adhesion of N-TER peptide-nucleic acid complexes followed by time-dependent uptake studies using confocal laser scanning microscopy (cLSM). To reveal the biological effect of miRNA-27a on adipocyte development after transfection treatment, Oil-Red-O (ORO)- staining was performed to estimate the degree of in lipid droplets accumulated ORO in mature adipocytes by using light microscopy images as well as absorbance measurements.Results: The present findings demonstrated that amphipathic N-TER peptides represent a suitable DDS for miRNAs by promoting non-covalent complexation through electrostatic interactions between both components as well as cellular adhesion of the N-TER peptide – nucleic acid complexes followed by uptake across cell membranes and intracellular release of miRNAs. The anti-adipogenic effect of miRNA-27a in 3T3-L1 cells could be detected in mature adipocytes by reduced lipid droplet formation.Conclusion: The present DDS assembled from amphipathic N-TER peptides and miRNAs is capable of inducing the anti-adipogenic effect of miRNA-27a by reducing lipid droplet accumulation in mature adipocytes. With respect to miRNA mimic replacement therapies, this approach might provide new therapeutic strategies to prevent or treat obesity and obesity-related disorders.Keywords: drug delivery system, DDS, miRNA-27a, amphipathic peptides, anti-adipogenic effect, 3T3-L1 cells
format	article
author	Schachner-Nedherer AL Werzer O Kornmueller K Prassl R Zimmer A
author_facet	Schachner-Nedherer AL Werzer O Kornmueller K Prassl R Zimmer A
author_sort	Schachner-Nedherer AL
title	Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
title_short	Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
title_full	Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
title_fullStr	Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
title_full_unstemmed	Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems
title_sort	biological activity of mirna-27a using peptide-based drug delivery systems
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/267a761fabaa4d5dac1fc4e29aff261b
work_keys_str_mv	AT schachnernedhereral biologicalactivityofmirna27ausingpeptidebaseddrugdeliverysystems AT werzero biologicalactivityofmirna27ausingpeptidebaseddrugdeliverysystems AT kornmuellerk biologicalactivityofmirna27ausingpeptidebaseddrugdeliverysystems AT prasslr biologicalactivityofmirna27ausingpeptidebaseddrugdeliverysystems AT zimmera biologicalactivityofmirna27ausingpeptidebaseddrugdeliverysystems
_version_	1718398652019376128

Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems

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