Research ArticleBioengineering

Cell-selective arrhythmia ablation for photomodulation of heart rhythm

Science Translational Medicine  28 Oct 2015:
Vol. 7, Issue 311, pp. 311ra172
DOI: 10.1126/scitranslmed.aab3665

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For heart cells only

Abnormal heartbeats, called arrhythmias, can be stopped by photoablation, but the use of light energy to terminate malfunctioning cardiomyocytes runs the risk of damaging the other dozen or so cell types in the heart. To be more specific in photoablation, Avula and colleagues devised a heart cell–targeted photosensitizer, which could be delivered systemically. Laser light was then used to ablate only cardiomyocytes while leaving the surrounding fibroblasts and other cells intact. The approach was tested in vivo in rodents and in sheep and rat hearts ex vivo, demonstrating that the technology is indeed able to avoid fibroblasts and block electrical conduction, returning the heart to its normal rhythm.

Abstract

Heart disease, a leading cause of death in the developed world, is overwhelmingly correlated with arrhythmias, where heart muscle cells, myocytes, beat abnormally. Cardiac arrhythmias are usually managed by electric shock intervention, antiarrhythmic drugs, surgery, and/or catheter ablation. Despite recent improvements in techniques, ablation procedures are still limited by the risk of complications from unwanted cellular damage, caused by the nonspecific delivery of ablative energy to all heart cell types. We describe an engineered nanoparticle containing a cardiac-targeting peptide (CTP) and a photosensitizer, chlorin e6 (Ce6), for specific delivery to myocytes. Specificity was confirmed in vitro using adult rat heart cell and human stem cell–derived cardiomyocyte and fibroblast cocultures. In vivo, the CTP-Ce6 nanoparticles were injected intravenously into rats and, upon laser illumination of the heart, induced localized, myocyte-specific ablation with 85% efficiency, restoring sinus rhythm without collateral damage to other cell types in the heart, such as fibroblasts. In both sheep and rat hearts ex vivo, upon perfusion of CTP-Ce6 particles, laser illumination led to the formation of a complete electrical block at the ablated region and restored the physiological rhythm of the heart. This nano-based, cell-targeted approach could improve ablative technologies for patients with arrhythmias by reducing currently encountered complications.

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