Nanoparticle Targeting May Revolutionize Cardiac Photoablation Therapy

By LabMedica International staff writers
Posted on 10 Nov 2015

A light-based therapeutic approach to correct cardiac arrhythmia has been improved by the development of a nanotechnique that allows precise delivery of photosensitive molecules to malfunctioning cardiomyocytes while avoiding normal cells.

Abnormal heartbeats, called arrhythmias, can be stopped by photoablation (light-induced killing), 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.

Image: Micrographs show a cardiac myocyte cell (top) and an attached fibroblast cell (bottom) in a rat heart, after the injection of the newly developed nanoparticle. In the second frame, red light has been applied. The red coloring indicates that the myocyte, which causes cardiac arrhythmia, has been killed, while the fibroblast remains unharmed (Photo courtesy of the University of Michigan).

To increase the precision of the photoablation procedure investigators at the University of Michigan (Ann Arbor, USA) engineered a type of nanoparticle containing a cardiac-targeting peptide (CTP) and a photosensitizer, chlorin e6 (Ce6), for specific delivery to myocytes. After uptake by myoctes, low energy laser light introduced through a catheter destroyed only the cells that had absorbed the nanoparticles, leaving the other heart cells unharmed.

The investigators reported in the October 28, 2015, online edition of the journal Science Translational Medicine that they confirmed the specificity of the method in vitro using adult rat heart cell and human stem cell–derived cardiomyocyte and fibroblast co-cultures. 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.

"In our cancer work, we used nanoparticles that were about 120 nanometers in size," said contributing author Dr. Raoul Kopelman, professor of chemistry, physics, and applied physics at the University of Michigan. "To work inside the heart, we needed to develop a particle that did the same job but was only six nanometers in size. The great thing about this treatment is that it is precise down to the level of individual cells. Drugs spread all over the body and high-power lasers char the tissue in the heart. This treatment is much easier and much safer."

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University of Michigan