<p>Biological Activity Of miRNA-27a Using Peptide-based Drug Delivery Systems</p>

Abstract

BackgroundEndogenously 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.MethodsIn 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.ResultsThe 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.ConclusionThe 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.

Bta-miR-376a Targeting KLF15 Interferes with Adipogenesis Signaling Pathway to Promote Differentiation of Qinchuan Beef Cattle Preadipocytes

“…Many regulatory factors associated with adipogenesis, as well as regulatory methods of epigenetics and miRNA, have been identified [ 28 , 29 , 30 , 31 ]. Several novel miRNA have been identified using microarray analysis and high-throughput sequencing [ 32 ]: miR-424 [ 33 ], miR-210 [ 34 ], miR-26a [ 35 ], miR-17-5p [ 36 ], miR-152 [ 37 ], miR-143 [ 38 ], and miR-519d [ 39 ] reduce adipogenesis by positively facilitating adipocyte differentiation, whereas miR-20a-5p [ 40 ], miR-130a/b [ 23 ], miR-27a/b [ 41 , 42 ], and miR-155 [ 43 ] negatively regulate adipocyte differentiation. The expression of bta-miR-376a differs among bovine tissues and is tissue-specific.…”

Use of Protamine in Nanopharmaceuticals—A Review

“…Nanoscaled preparations like nanoparticles or liposomes incorporating CPPs are getting more and more popular because of their ability to deliver macromolecules as well as forming nanoplexes [97]. DNA as well as RNA nanotechnologies have become an interdisciplinary research field where researchers from pharmaceutical sciences, chemistry, physics, medicine and computer science are coming together to overcome obstacles and find solutions for future challenges [51,[98][99][100].…”

“…technologies have become an interdisciplinary research field where researchers pharmaceutical sciences, chemistry, physics, medicine and computer science are c together to overcome obstacles and find solutions for future challenges [51,[98][99][100] With respect to nanoparticles, several physicochemical parameters are essen predicting their application potential in vitro and in vivo and for their use in future maceutical strategies. In Figure 2, an overview on how physicochemical properti influence the biodistribution in several organs is given.…”

Protamine – A Review on an Oligonucleotide-Binding Peptide Applied in Nanopharmaceuticals including Vaccines

“…Nanoscaled preparations like nanoparticles or liposomes incorporating CPPs are getting more and more popular because of their ability to deliver macromolecules as well as forming nanoplexes (Dul et al 2015). DNA as well as RNA nanotechnologies have become an interdisciplinary research field where researchers from pharmaceutical sciences, chemistry, physics, medicine and computer science are coming together to overcome obstacles and find solutions for future challenges (Schachner-Nedherer et al 2019;Vogel et al 2005;Palazzolo, Hadla, Spena, Caligiuri, et al 2019;Palazzolo, Hadla, Spena, Bayda, et al 2019).…”