Bio-medical gold rush
Intrigued by the power of light, Prof. Dror Fixler, an expert in electro-optics and photonics, describes several theranostic methods developed over the past few decades. “At some point, medical researchers went for the gold, utilizing the high visibility and high-penetration depth of gold nanoparticles in the body”, he explains.
Prof. Fixler is a lecturer at the Faculty of Engineering and a member of the Institute of Nanotechnology and Advanced Materials (BINA) at BIU, who invents bio-compatible sensing and detection applications for biomedicine, cosmetics, food, military, and other industries.
A detection tool for breast cancer which Fixler took part in its development together with a team at UCLA, utilized the intense light absorption of tissues to differentiate between cancerous and noncancerous tissue. “This system, however,” explains Fixler, “though highly sensitive, was also non-selective, and required further refinement before showing promising results."
“Interestingly,” he says, “other theranostic tools based on gold nanoparticles demonstrated the opposite challenge: although highly selective, they lacked high-sensitivity - unable to show high concentrations of particles in the body.”
Arterial blockages: Rounding up the usual suspects
Combining the two approaches to gain the best of both worlds, Fixler and his lab team, used a technique of coating gold nanorods (GNRs) with epidermal growth factor receptor (EGFR) inhibitors to treat melanoma, tongue cancer, and cancer of the vocal-cords. It was in early 2014 when he would shine a bright light at the end of the tunnel with a ground-breaking treatment for atherosclerosis
, a disease that affects millions worldwide.
Atherosclerosis is caused by the accumulation of fibro-fatty plaque which thickens the artery walls and often results in increased pulse pressure. While some patients can live an entire lifetime with narrowed arteries, others suffer severe arterial malfunction which can cause blood-clots, heart-attack or even a stroke.
Having recognized the unresolved challenge of pinpointing those narrowed arteries likely to cause a blockage, Prof. Fixler describes, “We knew that highly inflamed cells appear in areas of active artery blockages, and that these areas typically increase the risk of a stroke. However, there was no effective detection method for mapping cell concentrations and identifying blood clots,” he says.
Macrophages swallow the gold bait
Determined to find a solution, Fixler’s team at BIU joined forces with cardiology researchers at the Rabin Medical Center in Petach-Tikva in a study to pinpoint active artery blockages in highly inflamed areas. To evaluate abnormalities and changes in function, doctors would require a complete image of a specific tissue and its surroundings.
The Diffusion-Reflection (DR) technique was chosen as the most suitable candidate, with gold nanorods serving as contrast agents for deep-volume imaging. With this non-invasive diagnostic method they could measure the reflected light intensity profile of the tissue at several distances, and gain invaluable morphological information.
Amazingly, when gold nanorods were inserted in the body, they began to cling to inflamed cells on the artery walls. “We saw that the gold particles adhered to macrophages, which are white blood cells located in the inflamed areas.” explains Fixler. “Inflammatory cells - the main component of active atherosclerotic plaques which usually appear in the pathology of such arteries – engulfed and digested the gold nanoparticles. The gold particles remained intact as glowing clusters, marking problem areas where blood clots are likely to develop.”
The team took this research a step further. “By attaching a ‘good’ type of HDL anti-cholesterol drug to the gold nanoparticles, the gold is used as bait, which we can easily track. The macrophage cells identify the gold particles and swallow them along with the medication. The medication remains in the inflamed area and starts working”, Fixler says proudly. “This enabled us to completely cure a lab rat from an advanced stage of atherosclerosis.”
So far, this breakthrough medical technology has succeeded only in animals, but the doctors that collaborated with Fixler are confident that it will prevent many strokes in humans in the not-so-distant future.
Story originally published in Institute for Nanotechnology and Advanced Materials' summer 2016 newsletter