Document Detail

Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?
MedLine Citation:
PMID:  23140503     Owner:  NLM     Status:  Publisher    
Aim: To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. Materials & methods: Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp. Results: Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. In contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50-250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores. Conclusion: The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias. Original submitted 8 March 2012; Revised submitted 12 July 2012.
Michele Miragoli; Pavel Novak; Pakatip Ruenraroengsak; Andrew I Shevchuk; Yuri E Korchev; Max J Lab; Teresa D Tetley; Julia Gorelik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-12
Journal Detail:
Title:  Nanomedicine (London, England)     Volume:  -     ISSN:  1748-6963     ISO Abbreviation:  Nanomedicine (Lond)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101278111     Medline TA:  Nanomedicine (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Myocardial Function Unit, National Heart & Lung Institute, Imperial College London, 4th floor, Imperial Centre for Translational & Experimental Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
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