Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes
Anna-Laurence Schachner-Nedherer,
Julia Fuchs,
Ivan Vidakovic,
Oliver Höller,
Gebhard Schratter,
Gunter Almer,
Eleonore Fröhlich,
Andreas Zimmer,
Martin Wabitsch,
Karin Kornmueller,
Ruth Prassl
Affiliations
Anna-Laurence Schachner-Nedherer
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Julia Fuchs
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Ivan Vidakovic
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Oliver Höller
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Gebhard Schratter
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Gunter Almer
Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria
Eleonore Fröhlich
Center for Medical Research, Medical University of Graz, 8010 Graz, Austria
Andreas Zimmer
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria
Martin Wabitsch
Division of Pediatric Endocrinology, Diabetes Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany
Karin Kornmueller
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
Ruth Prassl
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, 8010 Graz, Austria
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 PPARγ 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.
