Nanoparticle Detonations May Be Able to Burn Vascular Plaques

Reed Miller

March 14, 2010

March 14, 2010 (Atlanta, Georgia) — A biophotonic technique adapted from oncology for precise "burning" of tissue may someday be used to treat atherosclerotic plaque.

A group of researchers from Russia and the Netherlands is developing techniques for delivering silica-gold nanoparticles, 80 nm in radius, to atherosclerotic coronary plaques. When exposed to near-infrared laser, the particles "detonate" and heat up to 50˚C to 150˚C, while surrounding tissue stays below 40˚C.

Dr Alexandr Kharlamov

"Our skin is transparent for infrared light, and it means that we can focus on a narrow spot, and when this radiation goes to the nanoparticles, it's like a detonation--like a small balloon--it burns like plasma," Dr Alexandr Kharlamov (Urals State Medical Academy, Ekaterinburg, Russia) explained in a conversation with heartwire .

In addition to destroying the plaque, the burning particles may also create vapor bubbles in the cytoplasm of the cells and boiling of fluid in the intracellular spaces or cause acoustic waves that could cause inflammation in the vessel wall. This damage may promote valuable healing of the vessel wall, but the technique will have to be refined to ensure that the damage does not promote too much inflammation or thrombosis, perhaps by accompanying the nanoparticles with some combination of anti-inflammatory or antithrombotic drugs, Kharlamov said.

Here at the American College of Cardiology 2010 Scientific Sessions, Kharlamov's team is presenting data from a 27-patient controlled study of different nanoparticle-delivery methods. In the trial, a control group of 10 patients got just a saline solution. A second group was treated with nanoparticles placed directly into the site of the plaque via ultrasound-mediated albumin-coated gas-filled microbubbles coated with surface antibodies. In the third group of patients, nanoparticles were delivered to the plaque by circulating progenitor cells, similar to adult stem cells. The nanoparticles were exposed to the catheter-delivered laser three days after implant. All patients were given antithrombotic therapy.

On average, the progenitor-cell technique destroyed about 97% of the plaque and the microbubble technique destroyed 64.1% of plaque. Revascularization was achieved in all of the patients. The plaque's fibrous cap was destroyed in all the patients in both groups. Also, in the progenitor-cell group, intravascular ultrasound showed total degradation of the plaque's typical structure, the researchers report.

So far, the patients in the study have shown no complications within a year of the procedure, including no restenosis. However, animal data suggest that obliteration of the fibrous cap could lead to fatal atherothrombosis.

Kharlamov said his group plans to complete more experiments in pigs before proceeding with more clinical trials. The researchers are still trying to fully understand the local biophysical response of heating the tissue so they can pinpoint the ideal level of energy to deliver to the plaque site while also controlling the risk of thrombosis. He also pointed out that access to progenitor cells is difficult in most countries, and this might hinder the long-term development of the technology.