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Innovative nanoparticle formulation for a miR-133 based treatment of cardiac hypertrophy

Periodic Reporting for period 1 - miRCaP (Innovative nanoparticle formulation for a miR-133 based treatment of cardiac hypertrophy)

Reporting period: 2016-12-01 to 2018-05-31

MicroRNAs (miRs) are regulators involved in several biological processes and have been recognized as potential novel therapeutic targets for the treatment and prevention of cardiovascular diseases (CVDs). In particular, the muscle-specific miR-133, which is inversely related to failing heart conditions, is involved in several aspects of pathological cardiac remodelling via mitigation of cardiac hypertrophy and fibrosis, fine-tuning of the 1-adrenergic receptor signalling and protection against oxidative stress-mediated apoptosis. However, effective and clinically oriented interventions aimed at the delivery miR-133 mimics for preventing the stress-induced downregulation of miR-133 levels are still missing.
The answer to this problem consisted here in the evaluation of an unconventional strategy for the non-invasive and nanoparticle-based delivery of therapeutic miR-133 mimics to the diseased heart. In the first part of the project, calcium phosphate-based nanoparticles (CaPs) loaded with miR mimics were generated and assessed for quality and stability. Then, activities were dedicated to the evaluation of miR-CaP biocompatibility and delivery of miR mimics to the heart. Subsequently, the research plan continued with assessment of delivery of miR-133 mimic to diseased heart and evaluation of the therapeutic effect.