title: Enhanced delivery of microRNA mimics to cardiomyocytes using ultrasound responsive microbubbles reverses hypertrophy in an in-vitro model.
abstract: 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.
authors.affiliation: Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland Trinity Centre for Bioengineering, Trinity College Dublin, College Green, Dublin, Ireland.
authors.forename: Sarah-Louise
authors.initials: SL
authors.lastname: Gill
authors.affiliation: Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland Trinity Centre for Bioengineering, Trinity College Dublin, College Green, Dublin, Ireland.
authors.forename: Hugh
authors.initials: H
authors.lastname: O'Neill
authors.affiliation: Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland Trinity Centre for Bioengineering, Trinity College Dublin, College Green, Dublin, Ireland.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: McCoy
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Suhanniya
authors.initials: S
authors.lastname: Logeswaran
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: O'Brien
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Alice
authors.initials: A
authors.lastname: Stanton
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Helena
authors.initials: H
authors.lastname: Kelly
authors.affiliation: Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland Trinity Centre for Bioengineering, Trinity College Dublin, College Green, Dublin, Ireland.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Duffy
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000628:therapy; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D066298:In Vitro Techniques; D008081:Liposomes / Q000627:therapeutic use; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000627:therapeutic use; D045423:Microbubbles / Q000627:therapeutic use*; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000000981:diagnostic imaging / Q000187:drug effects*; D014162:Transfection / Q000379:methods; D014463:Ultrasonography
chemical_list: D008081:Liposomes; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse
keywords: cardiomyocytes; heart failure; microRNA; microbubbles; ultrasound