New nanoparticle developed at University could prevent cardiac issues

Thursday, November 5, 2015 - 4:01pm

A new nanoparticle developed at the University may prove key to treating a condition that affects nearly 4 million Americans a year.

As part of a five-year ongoing study, a University research team announced in late October that they had created a nanoparticle — a microscopic particle with at least one dimension measuring 100 nanometers or less — that could be essential to a targeted therapy for cardiac arrhythmias. Cardiac arrhythmias are caused by malfunctions in certain heart muscle cells that lead to erratic heart beats and may eventually cause heart attacks or strokes. The new technique developed uses nanotechnology to more precisely target and destroy the cells within the heart that cause cardiac arrhythmias.

The findings of the study are detailed in a new paper in the journal Science Translational Medicine.

Currently, cardiac arrhythmias are usually treated with drugs or with radiofrequency cardiac ablation, a procedure that burns away malfunctioning cells using a laser. Both drugs and ablation are effective treatments, but they can result in unintended damage to surrounding cells.

“It’s almost like you are bombing the heart with the laser,” said Jerome Kalifa, an assistant professor at the Medical School and one of the lead researchers in the study. “Right now, we can only target the general area, so there is collateral damage.”

The new nanoparticle treatment was successful in studies conducted on rodents and sheep. Researchers found they were able destroy malfunctioning cells more precisely using nanoparticles activated by low-level red light illumination, as opposed to the traditional high-powered laser.

The treatment is a modified version of a technique currently used in cancer treatment, where doctors mark target cells with a chemical that makes them sensitive to low-level red light, according to Uma Mahesh Avula, a postdoctoral research fellow and member of the research team. The light destroys only the marked cells, leaving the surrounding cells and tissue unharmed.

“With this study, we developed a specific nanoparticle that targets a very specific cell type: cardiac myocytes,” Avula said.

Cardiac myocytes are a type of heart muscle cell that have been linked to the development of cardiac arrhythmias. Kalifa said the specificity of the nanoparticle in targeting these cells allows for more flexibility in treatment, decreased complications, and increased protection of structures within and around the heart.

“The goal of this project was to adapt the tools that are working well for cancer cells so that they can recognize cardiac cells that initiate and habituate cardiac arrhythmias,” he said.

The team initially tried using nanoparticles the same size as those used for cancer treatment, which are about 120 nanometers in size. That approach, Avula said, was unsuccessful, leading to the team’s main challenge — figuring out what size of nanoparticle to develop. Ultimately, they settled on a smaller size, developing a particle that was only six nanometers in size.

Chemistry Prof. Raoul Kopelman, who led the team, said the size they ended up with was small even by nanotechnology standards.

“The weight of one human hair is 80 microns,” he said. “These particles are over 10,000 times smaller than that.”

Within the tiny particle, an amino acid that causes the particular to target myocytes, as well as a chemical that makes the particle light sensitive and another chemical to shield it from the immune system. During the study, the nanoparticles were injected into the heart and absorbed by the target cell. Low-level red light was then used to destroy only the cells with the nanoparticles in them.

“This technology allows us to simplify the procedure for treating cardiac arrhythmias, make it more efficient, and safer,” Kalifa said.

The next step for the research team will be to replicate their successful results on rodents and sheep in a trial with humans. The researchers are also working to develop a method for producing larger amounts of the nanoparticles at pharmaceutical grade standards.

“This is one of the first times that a targeted therapy for arrhythmias has been developed,” Kalifa said. “It will be a while still, but should we have the right resources, we could contribute significantly to improving treatment for patients with arrhythmias.”

Kopelman, who has the disease he is targeting, said the cross-disciplinary research between material chemistry and cardiology represented an exciting step forward in the field and for him personally.

“I have been suffering from heart arrhythmias since age 11, so it has always been my ambition to do something about it,” he said.