Knockdown of Gene Expression in Macrophages by microRNA Mimic-Containing Poly (Lactic- co -glycolic Acid) Microparticles

microRNA (miRNA) regulate target gene expression through translational repression and/or mRNA degradation and are involved in the regulation of inflammation. Macrophages are key inflammatory cells that are important in chronic inflammatory lung diseases such as cystic fibrosis (CF). Macrophage-expre...

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Veröffentlicht in:Medicines (Basel, Switzerland) Switzerland), 2018-12, Vol.5 (4), p.133
Hauptverfasser: McKiernan, Paul J, Lynch, Patrick, Ramsey, Joanne M, Cryan, Sally Ann, Greene, Catherine M
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Sprache:eng
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Zusammenfassung:microRNA (miRNA) regulate target gene expression through translational repression and/or mRNA degradation and are involved in the regulation of inflammation. Macrophages are key inflammatory cells that are important in chronic inflammatory lung diseases such as cystic fibrosis (CF). Macrophage-expressed miRNA represent therapeutic drug targets, yet delivery of nucleic acids to macrophages has proved challenging. miRNAs were encapsulated in poly (lactic- -glycolic acid) (PLGA)-based microparticles using double emulsion solvent evaporation and characterised for physicochemical features. Phorbol myristic acetate (PMA)-differentiated U937 macrophages were transfected with empty PLGA microparticles or those encapsulating a premiR-19b-3p or scrambled control miRNA mimic. miRNA internalisation and knockdown of a miR-19b-3p target gene, secretory leucoprotease inhibitor (SLPI), were determined by qRT-PCR. Microparticle formulations were consistently found to be 2⁻3μm and all had a negative ζ potential (-5 mV to -14 mV). Encapsulation efficiency of premiR-19b-3p was 37.6 ± 13.4%. Levels of mature miR-19b-3p were higher in macrophages after delivery of premiR-19b-3p microparticles compared to empty or scrambled control miRNA-containing microparticles. Significant SLPI knockdown was achieved 72 hours post-delivery of premiR-19b-3p microparticles compared to controls. : miRNA-encapsulating PLGA microparticles offer a new treatment paradigm for delivery to macrophages that could potentially be administered to CF lungs via inhalation.
ISSN:2305-6320
2305-6320
DOI:10.3390/medicines5040133