Peer-Reviewed Journal Details
Mandatory Fields
Gill, SL;O'Neill, H;McCoy, RJ;Logeswaran, S;O'Brien, F;Stanton, A;Kelly, H;Duffy, GP
2014
January
Technology And Health Care
Enhanced delivery of microRNA mimics to cardiomyocytes using ultrasound responsive microbubbles reverses hypertrophy in an in-vitro model
Published
WOS: 9 ()
Optional Fields
GENE DELIVERY HEART-FAILURE DRUG-DELIVERY CELLS TRANSFECTION PERSPECTIVES COMBINATION INHIBITION EXPRESSION DISEASE
22
37
51
BACKGROUND: Cardiovascular diseases (CVD) account for 36% of deaths in Europe and the United States. Gene therapy can act as a therapeutic modality for the treatment of CVD. The use of microRNA mimetics may be advantageous as they regulate important processes in health and pathology. A major hurdle for using miRNA therapies relates to site specific delivery and sufficient cellular uptake of material to achieve efficacy. OBJECTIVE: To assess the feasibility of ultrasound responsive microbubble mediated delivery of miR mimics to cardiomyocytes. METHODS: Liposome/microbubble formulations were added to HL-1 cardiomyocytes in the presence/absence of ultrasound (US). Transfection efficacy and functionality was assessed using epifluorescent microscopy, flow cytometry and qRT-PCR. DNA Quantification post-ultrasound mediated transfection of HL-1s using microbubbles was quantified. The capability of miR-133 microbubble formulations to suppress hypertrophy were measured by quantifying changes in cell size. RESULTS: Ultrasound mediated microbubble formulations enhanced intracellular delivery of miR mimics in cardiomyocytes. Both complexed/encapsulated miR-microbubble formulations delivered functional miR mimics and showed no adverse effect on cardiomyocyte viability. Furthermore, ultrasound mediated microbubble transfection of miR-133 mimics reversed cardiomyocyte hypertrophy in an in-vitro model. CONCLUSIONS: This novel delivery method has the potential for further development as a targeted delivery strategy for miR therapeutics to the heart.
0928-7329
10.3233/THC-130772
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