Researchers at the University of Rhode Island are pioneering a novel treatment for Alcohol-Related Liver Disease (ARLD) using microscopic nanoparticles. Under the direction of Associate Professor Jyothi Menon, this pioneering treatment attempts to stop the inflammation and scarring caused by the illness in its tracks. Current management focuses primarily on reducing alcohol consumption and the use of anti-inflammatory drugs. Simultaneously, Menon’s team is investigating a treatment that would offer patients more than symptomatic relief.
As more than 1.5 billion people around the globe currently live with chronic liver diseases, the need for better treatments is more urgent than ever. Menon’s nanoparticles, engineered to target specific liver cells, could revolutionize treatment options for ARLD and potentially other conditions characterized by inflammation and fibrosis.
The Science Behind the Nanoparticles
To deliver the nucleic acid therapeutics in his research, Menon’s team has made nanoparticles that are about a thousand times smaller than the diameter of a human hair. This small size presents their unique ability to precisely penetrate targeted areas within the liver. By using the Kupffer cell-specific targeting moiety, the nanoparticles are preferentially absorbed in Kupffer cells. These immune cells are key players in the liver’s response to injury.
In normal livers, Kupffer cells in a context-dependent manner work to prevent inflammation. In the patients with ARLD, these beneficial cells directly or indirectly pump out increasing amounts of inflammatory protein signalling that increases inflammation and drives scarring. Menon’s research is the first to take this precise, targeted approach to pioneer that effort. What makes it unique is that there was no precedent literature to inform their initial efforts.
“As one of the first groups to even approach something like this using nanoparticle-based drug delivery systems, there wasn’t any sort of prior literature to help us figure out what roadblocks there could be when we took up this research,” – Dr. Jyothi Menon
The nanoparticles are specifically engineered to intervene earlier in the inflammatory process. Instead of going directly to the scar-producing cells, they go to the Kupffer cells to dampen their damaging signals.
“Instead of going for the cells which are producing the scar tissue, we’re going one step behind and targeting the Kupffer cells themselves so that we can prevent them from stimulating other cells in the liver and causing this fibrosis progression,” – Dr. Jyothi Menon
Promising Results and Broader Applications
Early findings from Menon’s studies suggest these nanoparticles have been effective in controlling scarring and inflammation. Oil red O staining validated reduced lipid droplet accumulation in ARLD-affected livers after nanoparticle treatment. Such a result is notable especially since lipid accumulation is a characteristic feature of hepatotoxicity.
Bucking menon’s research shows that the different parts of the nanoparticles didn’t have much of a therapeutic effect when tested on their own. Yet, when put together into one cohesive formulation, they had an extraordinary impact.
“But when we gave our final formulation with everything combined, it reduced inflammation and lipid droplet formation seen due to fat buildup in the liver. It was the combination of all of these things that actually had an effect,” – Dr. Jyothi Menon
These discoveries, which were published in the journal Biomaterials, were an important breakthrough in the continuing development of nanoparticle therapies. Menon emphasized their formulations suitability for multiple applications. As inflammation and fibrosis occur across many organs, he recommended that they be tailored for other inflammatory/fibrotic conditions.
“Our formulations are versatile, so they can be adapted or modified for treating other kinds of inflammation and fibrosis in other organs,” – Dr. Jyothi Menon
Implications for Future Research
The implications of Menon’s research go beyond ARLD. With chronic liver disease affecting billions around the world, innovation in targeted, disease-modifying therapies have the potential to upend existing treatment paradigms. As far as nanoparticle technology goes, there are many exciting and promising applications within medicine. It paves the way for unique approaches to address diseases characterized by comparable inflammatory mechanisms.
The team at the University of Rhode Island continues to work diligently on refining their nanoparticle formulations and evaluating their efficacy in broader contexts. They are not only tackling an unfamiliar frontier in nanoparticle-based therapies. With sustained efforts, their work just might give patients struggling with liver diseases and other inflammatory disorders a new lease on life.