Dr Prabhas Moghe, Rutgers University at New Brunswick
One person in every three is affected by heart disease and strokes, which are caused by our arteries becoming clogged with deposits of cholesterol. This builds up inside cells called macrophages that accumulate in the walls of damaged blood vessels. Now a team of scientists in America have developed nanoparticles that can be injected into the bloodstream, where they home in on areas where blockages are destined to occur and stop the buildup of cholesterol. Prabhas Moghe explained the study to Chris Smith...
Prabhas - Our technology is focused on developing a nanoparticle which can then reach the sites of these lesions and then block the uptake of the lipoproteins, the bad cholesterol, as they say, within the lesions. And here is where it gets very interesting because the primary character in this entire cascade is a macrophage which is an inflammatory blood cell whose job it is to clear out these lipoproteins. It’s only when this process gets out of control that the macrophages tend to become inflammatory and then recruit more blood cells and essentially lead to this festering of the lesion.
Chris - I see. So, when one has damage to a blood vessel, some fats can move into the damaged site and also, some cells, macrophages go in there, initially “intending” to clear up the mess. But actually, what then is happening is that they're making an inflammatory damaged area which in and of itself then attracts more fat to go in. S o, you almost have a self-fulfilling prophecy, if you've got damage, you get more damage and this grows and slowly blocks a blood vessel up. You've made nanoparticles that can home-in on these sites and arrest the process of this growth of this plaque.
Prabhas - Yeah, you're spot on.
Chris - So, how do they do that? What are the nanoparticles doing?
Prabhas - The way that we’ve designed these nanoparticles was to have a high affinity to certain molecules that the inflamed macrophages express to counteract how the fats might have a way to get into the cells.
Chris - So in essence, you have got a particle which pretends to be one of the bad fats that would normally go into and damage the wall of the blood vessel and it gets in the way, stopping the bad fats from being taken up by these macrophages at these sites. So, it should stop the plaque from getting any bigger.
Prabhas - That's right.
Chris - How do you know this works and how have you proved it?
Prabhas - In this paper, we have moved from taking the lab work in vivo using animals that have a high propensity to develop heart disease. You can take these animals, give them a suitable dose of the nanoparticles, and what was exciting, these articles, not only homed-in on the sites of these lesions but also, the animals that were treated showed a significant reduction in the amount of fat that was deposited in these blood vessels. And there was a significant reduction in the obstruction.
Chris - Are these particles likely to have some side effects?
Prabhas - I'm optimistic that the safety profiles look strong. Of course, this is something that we all have to verify using longer term studies. So, that will be the part of developing this technology. We have tried this out in the conventional smaller animals. Some of which tend to be very sensitive to these nanoparticles and yet, the animals have shown no sign of adverse events, as you will. I'm hopeful that these molecules are well-tolerated, particularly because they degrade into molecules that are basically secreted outside the body.
Kat - Prabhas Moghe. He’s from Rutgers University in the US.