Omega-3 fatty acids could unlock a new nanomedicine approach for treating ARDS
核心洞察
Researchers at the University at Buffalo received a $2 million, four-year NHLBI grant to develop a safer, more effective ARDS treatment using omega-3 fatty acids.
The approach delivers DHA via liposome nanoparticles to neutrophils (搜索) in the lungs, where the LOX5/15 (搜索) enzyme converts it into inflammation-resolving molecules called resolvins (搜索).
ARDS affects more than 200,000 people annually in the U.S., with a mortality rate of 30–50%, and current steroid-based therapies are not always successful and raise infection risk.
Lung inflammation and injury can quickly progress to acute respiratory distress syndrome (ARDS) (搜索) in patients with pneumonia, COVID-19 and other conditions. Now, researchers at the University at Buffalo are investigating whether omega-3 fatty acids—the same molecules found in salmon and other fatty fish—could form the basis of a safer and more effective treatment for this severe lung disease.
ARDS affects more than 200,000 people annually in the United States, and of those, 30 to 50% die, according to Zhenjia Wang, PhD, SUNY Empire Innovation Professor in the School of Pharmacy and Pharmaceutical Sciences at the University at Buffalo. "In the United States alone, the mortality rate is unacceptably high. ARDS also represents a major economic burden for health care systems," Wang says.
Wang recently received a $2 million, four-year grant from the National Heart, Lung and Blood Institute (NHLBI) (搜索) of the National Institutes of Health to pursue this research. He is collaborating with Elsa Bou Ghanem, PhD, associate professor in the Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB.
An unmet need in ARDS treatment
Current therapeutic options for ARDS remain limited. "Besides ventilation and draining fluid from the lungs, the only therapies currently used for this condition are anti-inflammatory drugs like steroids to blunt the inflammation," Wang notes. "These aren't always successful and make patients more susceptible to secondary infections."
This limitation underscores the need for approaches that can calm inflammation without compromising the immune system's ability to fight infection. "Acute lung inflammation/injury (ALI) is a dysregulated inflammation disease, and it quickly precipitates to the more severe ARDS," Wang explains.
Harnessing the body's own healing molecules
The researchers' strategy centers on neutrophils (搜索), a type of white blood cell that plays a central role in ARDS. "Neutrophils play a central role in ARDS, and targeting neutrophils using nanotechnology could impact the development of new therapeutics," says Bou Ghanem, who has expertise in immunology and neutrophils.
The approach builds on the body's natural anti-inflammatory machinery. "A lot of people take omega-3 supplements to help prevent vascular diseases because omega-3 fatty acids are effective at combatting inflammation," Wang says. "Recent studies show that the body converts one type of omega-3 fatty acid, DHA (docosahexaenoic acid), into healing molecules called resolvins (搜索). They are called this because they can resolve the inflammation, encourage healing and allow the immune system to keep fighting infections."
While resolvins (搜索) RvD1 and RvD2 show potential for calming inflammation in laboratory studies, it has proven difficult to manufacture a drug using these compounds due to stability issues, Bou Ghanem notes.
A nanoparticle delivery strategy
To overcome this challenge, Wang's hypothesis is to deliver DHA into neutrophils (搜索) that then stick to the blood vessels in the lungs using fat-based particles called liposomes. The specific LOX5/15 (搜索) enzyme then converts DHA into the resolvins (搜索). This process, in effect, makes resolvins directly in the inflamed lungs.
To test this, the researchers will use mice with acute lung injury models and give them nanoparticles with the hope of healing the injuries. They have three main goals: first, to develop the best liposomes for delivering DHA directly to neutrophils (搜索); second, to determine whether those neutrophils actually produce more resolvins (搜索) after receiving DHA; and third, to see whether this treatment improves ARDS in the animal studies.
Broader implications for inflammatory disease
If this strategy works, it could represent a completely new way of treating inflammatory diseases and conditions beyond ARDS, including some autoimmune diseases, arthritis, and Crohn's disease, Wang says, adding that in all diseases and conditions associated with inflammation, neutrophils (搜索) play a central role.
"If we can target the neutrophil using our nanoparticles, we can treat most inflammatory disease," he says. "The success of this application would be a paradigm shift."