Nanoparticles offer new hope for treating alcohol-related liver disease

Worldwide, more than 1.5 billion people suffer from chronic liver disease. The U.S. Centers for Disease Control and Prevention reports that it kills more than 52,000 people a year in the United States alone—the ninth most common cause of death in the country.

Despite this significant impact on society, alcohol-related liver disease (ARLD) remains largely unexplained by medical research. Texas A&M University researcher Dr. Jyothi Menon aims to change that with a promising new treatment she is developing. Her findings were recently published in Biomaterials.

Liver diseases are increasing rapidly around the world and there is a significant risk that they will slowly develop into more dangerous conditions such as cancer. Being able to use our technologies to develop effective solutions against this evolution is what drives me and is driving this research.”

Dr. Jyothi Menon, Associate Professor, Department of Biomedical Engineering, Texas A&M University

While current treatments for ARLD focus on stopping alcohol and anti-inflammatory drugs, Menon and her colleagues at the University of Rhode Island are taking a much more focused approach. They have developed tiny nanoparticles that are a thousand times smaller than the diameter of a human hair. These safe and biodegradable nanoparticles can seek out and attach to damaged liver cells. By binding to cells, the nanoparticles help them stop fueling disease progression.

In healthy people, the liver is a naturally self-healing organ, able to regenerate most of its function even when 70% to 80% is damaged. A key part of this healing process involves immune cells called Kupffer cells that protect the liver from infection and harmful substances. In a healthy liver, they also produce proteins that promote an anti-inflammatory response in other liver cells.

In chronic liver disease, when liver damage progresses and repeated injury occurs, the organ’s self-repair functions are also destroyed. Then, the liver involuntarily begins to damage itself. Kupffer cells, which previously fought inflammation, begin releasing protein signals with the opposite effect—increasing inflammation and encouraging other liver cells to form scar tissue in a process called fibrosis.

The result is life-threatening organ dysfunction and even fatal liver cancer.

The Menon lab’s nanoparticles are designed to stop this destructive process. Their surface is designed to recognize and bind selectively to a protein found only on Kupffer cells in the liver, allowing them to avoid other types of liver cells. This protein acts as a receptor on the cell membrane, receiving chemical signals and triggering cellular behaviors in response. When activated by the nanoparticle coating, it promotes beneficial, anti-inflammatory behavior in Kupffer cells instead of increasing inflammation and scarring. Nanoparticles also release anti-inflammatory treatments as they break down, delivering the drug directly to the cells that need it most.

“Instead of going for the cells that produce the scar tissue, we go a step back and target the Kupffer cells themselves so we can prevent them from stimulating other cells in the liver and causing this progression of fibrosis,” Menon said.

The result is much greater than the sum of its parts.

“Individual ingredients alone did not have much of a therapeutic effect,” Menon said. “But when we gave our final formulation with everything combined, it reduced inflammation and the formation of lipid droplets due to fat accumulation in the liver. It was the combination of all these things that really worked.”

Getting to this point was no easy feat. Because Menon’s group is one of the first to attempt this kind of approach, there was no prior research to back it up.

“As one of the first groups to even approach this using nanoparticle-based drug delivery systems, there was no previous literature to help us understand what obstacles there might be when we started this research,” Menon said. “The first time we were able to confirm that these particles can target Kupffer cells, it was very exciting for us.”

While Menon is currently focused on alcohol-related liver disease, her nanoparticle treatments have much broader applications. Targeted nanoparticles could be the future of treating diseases in many parts of the body.

“What we have generated is promising preliminary work showing that this compound can selectively target a specific cell population in the liver to deliver therapies and may have a potentially significant impact on the treatment of chronic ARLD,” he said. “Our formulations are flexible, so they can be adapted or modified to treat other kinds of inflammation and fibrosis in other organs.”