Trojan Horse Therapy Targets Heart Disease without Harmful Side Effects
by Amanda Chase, PhD
September 17, 2024
A new advance in cardiovascular health research may hold potential for reducing heart attacks and strokes while avoiding severe side effects seen with other treatments. In a recent study published in Nature Communications, a team of researchers, including co-first authors Sharika Bamezai (Sarnoff Fellow), Yapei Zhang, and Manisha Kumari, along with senior authors Bryan Ronain Smith and Nicholas Leeper, Stanford Cardiovascular Institute member, demonstrated the effectiveness of a cutting-edge nanotherapy.
Heart disease caused by plaque build-up in the arteries is the leading cause of death in the United States. This plaque build-up, known as atherosclerosis, leads to chronic inflammation in the arteries, which increases the risk of heart disease and stroke. Despite advances in treatment, heart disease and stroke remain a significant public health concern. Therefore, there is a critical need for novel treatments that target chronic inflammation in those at risk for adverse clinical events. The challenge, however, is to develop treatments that can precisely target inflammation without compromising the body’s overall immune defenses.
Nanoparticle therapies aim to achieve precision with selective targeting. These tiny particles are designed to deliver treatment directly to the affected area, improving effectiveness and minimizing side effects. In their study, the researchers used specially designed nanoparticles, termed “Trojan horse” nanoparticles, to deliver an anti-inflammatory treatment directly to the inflamed area in the arteries. These nanoparticles were designed to reactivate the body’s natural process of removing diseased cells – a phenomenon known as ‘efferocytosis’ (Latin: to carry the dead to the grave). Efferocytosis is often impaired in atherosclerosis, and allows diseased, dying and dead cells to accumulate in the developing plaque. This not only permits the lesion to grow – which obstructs the artery and impairs blood flow – but also directly promotes the inflammation that frequently precedes heart attack or stroke.
The research team successfully scaled up the production of the nanoparticle without altering their properties. They used a large animal model of cardiovascular disease to further show that those nanoparticles retained the ability to specifically deliver therapies to inflamed macrophages, immune cells that play a critical role in clearing out harmful cells and substances from the body.
Once trafficked to the diseased blood vessel, these nanoparticles reactivated the removal of diseased cells, and quenched inflammation in the artery. Importantly, the authors also confirmed that the nanoparticle is a precision medicine approach that does not induce off-target effects on healthy tissues outside of the target area (such as the unwanted removal of normal cells outside of the plaque), confirming their potential use as a precision medicine approach.
These findings represent a significant step forward in developing safer and more effective treatment for heart disease, paving the way for human trials. If successful, this “Trojan horse” nanoparticle therapy could become a powerful tool in improving cardiovascular health for the millions of people at risk of heart attacks and stroke.
Sharika Bamezai
Nicholas Leeper, MD