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. By 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; Published online 12 November 201. © 2013 Future Medicine Ltd.

Functional interaction between charged nanoparticles and cardiac tissue: A new paradigm for cardiac arrhythmia? / Miragoli, Michele; Novak, Pavel; Ruenraroengsak, Pakatip; Shevchuk, Andrew I.; Korchev, Yuri E.; Lab, Max J.; Tetley, Teresa D.; Gorelik, Julia. - In: NANOMEDICINE. - ISSN 1743-5889. - 8:5(2013), pp. 725-737. [10.2217/nnm.12.125]

Functional interaction between charged nanoparticles and cardiac tissue: A new paradigm for cardiac arrhythmia?

MIRAGOLI, MICHELE;
2013

Abstract

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. By 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; Published online 12 November 201. © 2013 Future Medicine Ltd.
Functional interaction between charged nanoparticles and cardiac tissue: A new paradigm for cardiac arrhythmia? / Miragoli, Michele; Novak, Pavel; Ruenraroengsak, Pakatip; Shevchuk, Andrew I.; Korchev, Yuri E.; Lab, Max J.; Tetley, Teresa D.; Gorelik, Julia. - In: NANOMEDICINE. - ISSN 1743-5889. - 8:5(2013), pp. 725-737. [10.2217/nnm.12.125]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2817810
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