Joshua T Maxwell1,2,3, Inthirai Somasuntharam1, Warren D Gray1, Ming Shen2,3, Jason M Singer2,3, Bo Wang2,3, Talib Saafir2,3, Brian H Crawford2,3, Rong Jiang2,3, Niren Murthy4, Michael E Davis1,2,3, Mary B Wagner2,3. 1. Wallace H Coulter Department of Biomedical Engineering, Emory University School of Medicine, 1648 Pierce Dr NE, Atlanta, GA 30307, USA. 2. Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine, 1648 Pierce Dr NE, Atlanta, GA 30307, USA. 3. Children's Heart Research & Outcomes (HeRO) Center, Children's Healthcare of Atlanta & Emory University, Atlanta, GA, USA. 4. Department of Bioengineering, University of California Berkeley, Berkeley, CA, USA.
Abstract
AIMS: To evaluate the ability of N-acetylglucosamine (GlcNAc) decorated nanoparticles and their cargo to modulate calcium handling in failing cardiac myocytes (CMs). MATERIALS & METHODS: Primary CMs isolated from normal and failing hearts were treated with GlcNAc nanoparticles in order to assess the ability of the nanoparticles and their cargo to correct dysfunctional calcium handling in failing myocytes. RESULTS & CONCLUSION: GlcNAc particles reduced aberrant calcium release in failing CMs and restored sarcomere function. Additionally, encapsulation of a small calcium-modulating protein, S100A1, in GlcNAc nanoparticles also showed improved calcium regulation. Thus, the development of our bioactive nanoparticle allows for a 'two-hit' treatment, by which the cargo and also the nanoparticle itself can modulate intracellular protein activity.
AIMS: To evaluate the ability of N-acetylglucosamine (GlcNAc) decorated nanoparticles and their cargo to modulate calcium handling in failing cardiac myocytes (CMs). MATERIALS & METHODS: Primary CMs isolated from normal and failing hearts were treated with GlcNAc nanoparticles in order to assess the ability of the nanoparticles and their cargo to correct dysfunctional calcium handling in failing myocytes. RESULTS & CONCLUSION:GlcNAc particles reduced aberrant calcium release in failing CMs and restored sarcomere function. Additionally, encapsulation of a small calcium-modulating protein, S100A1, in GlcNAc nanoparticles also showed improved calcium regulation. Thus, the development of our bioactive nanoparticle allows for a 'two-hit' treatment, by which the cargo and also the nanoparticle itself can modulate intracellular protein activity.
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