Cell-selective arrhythmia ablation for photomodulation of heart rhythm.
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.
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Uma Mahesh R
UM
Avula
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Hyung Ki
HK
Yoon
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Chang H
CH
Lee
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Kuljeet
K
Kaur
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Rafael J
RJ
Ramirez
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Yoshio
Y
Takemoto
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Steven R
SR
Ennis
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Fred
F
Morady
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Todd
T
Herron
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
Omer
O
Berenfeld
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. kalifaj@med.umich.edu kopelman@umich.edu.
Raoul
R
Kopelman
Division of Cardiovascular Medicine, Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA. kalifaj@med.umich.edu kopelman@umich.edu.
Jérôme
J
Kalifa
D055011:Ablation Techniques / Q000379:methods*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry; D001145:Arrhythmias, Cardiac / Q000628:therapy*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000528:radiation effects; D010455:Peptides / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep
D000889:Anti-Arrhythmia Agents; D010455:Peptides; D017319:Photosensitizing Agents