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Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes

ORCID
0000-0002-4122-5762
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Schachner-Nedherer, Anna-Laurence;
ORCID
0000-0003-4576-615X
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Fuchs, Julia;
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Vidakovic, Ivan;
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Höller, Oliver;
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Schratter, Gebhard;
ORCID
0000-0003-3574-538X
Affiliation
Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria;
Almer, Gunter;
ORCID
0000-0002-6056-6829
Affiliation
Center for Medical Research, Medical University of Graz, 8010 Graz, Austria;
Fröhlich, Eleonore;
ORCID
0000-0003-3127-287X
Affiliation
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria;
Zimmer, Andreas;
ORCID
0000-0001-6795-8430
Affiliation
Division of Pediatric Endocrinology, Diabetes Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany;
Wabitsch, Martin;
ORCID
0000-0003-1039-9732
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Kornmueller, Karin;
ORCID
0000-0002-1010-9494
Affiliation
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria;(A.-L.S.-N.);(J.F.);(I.V.);(O.H.);(K.K.)
Prassl, Ruth

Obesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a) into a pegylated lipid nanoparticle (PEG-LNP) formulation by a single-step microfluidic-assisted synthesis step. For the miRNA-loaded LNPs, the following system properties were determined: particle size, zeta potential, miRNA complexation efficiency, and cytotoxicity. We have used a human preadipocyte cell line to address the transfection efficiency and biological effects of the miRNA candidates at the gene and protein level. Our findings revealed that the upregulation of miR27a in preadipocytes inhibits adipogenesis by the downregulation of PPARĪ³ and the reduction of lipid droplet formation. In contrast, miR26a transfection in adipocytes induced white adipocyte browning detected as the upregulation of uncoupling protein 1 (UCP1) as a marker of non-shivering thermogenesis. We conclude that the selective delivery of miRNAs by PEG-LNPs to adipocytes could offer new perspectives for the treatment of obesity and related metabolic diseases.

Category

Editor:
de Sousa, Fani Pereira; Valente, Joana
Published in:
Pharmaceutics  
Vol. 15, No. 7 (19.07.2023)
Volume:
15
No.:
7
Date Issued:
19.07.2023
DOI:
10.3390/pharmaceutics15071983
Language:
English
Type of Resource:
Text
Keywords:
microRNA; lipid nanoparticles; adipogenesis; automated quantitative image analysis
Subject of DNB:
610 Medical sciences Medicine
DDC:
615 Pharmakologie, Therapie

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License Holder: © 2023 by the authors.

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