- Obesity can lead to conditions such as type 2 diabetes, high blood pressure, stroke, and some cancers.
- Chronic, systemic inflammation is the causal link between obesity and the conditions that stem from it.
- A team of U of I researchers developed a unique targeted drug delivery method to treat inflammatory cells through the use of nanomedicine, in order to alleviate these conditions.
URBANA, Ill. - Obesity can lead to potentially life-threatening conditions such as high blood pressure (hypertension), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, some cancers, and clinical depression or anxiety.
With such an intense group of problems, treating obesity and the conditions that can result from it is a major health and economic imperative.
Kelly Swanson, a professor of nutrition and nutrigenomics in the Department of Animal Sciences at the University of Illinois, has been part of a team of researchers from across the U of I campus examining ways to alleviate these conditions. The team is led by Andrew Smith, a bioengineering assistant professor at U of I. Their work, published in a recent issue of ACS Nano, describes a unique approach the team developed that could point the way to innovative, highly effective treatments for those who suffer from obesity.
Over the last decade or so, medical research has shown that, in the obese state, adipose tissue (mostly made of fat cells) becomes enlarged and inflamed. This causes systemic inflammation, which is believed to be a causal link between obesity and the conditions that stem from it.
“In the obese state, there are a huge number of immune cells that get into the adipose [fat] tissue,” Smith says. “They wouldn’t normally be there in such large numbers, and their presence is what is responsible for this inflammation. These cell types that we talk about are called macrophages.”
These macrophages are white blood cells that are a typical part of a healthy body and perform such important functions as detecting, engulfing and destroying foreign substances. In an obese body, these macrophages enter the adipose tissue in large numbers and their behavior changes: They become inflamed.
“That means they are telling the body that something is wrong,” Smith says. “They secrete molecules that cause a response throughout the entire body.”
With the knowledge of how these macrophages work, Smith wanted to find a way to shut down their inflammatory response. He and his team developed a unique way to attack the problem through nanomedicine.
Usually nanomedicine involves targeted treatments for diseased tissue like a tumor that constitutes only a very small part of the body. In this case, the adipose target is physically much larger, and it is found surrounding the organs in the peritoneal cavity (where the digestive system is located). The goal was to evaluate treatments injected into the peritoneal cavity to determine if they were able to reduce inflammation.
U of I bioengineering assistant professor Wawrzyniec Dobrucki oversaw the PET/CT imaging, image processing, and analysis in the studies.
“Using noninvasive imaging approaches, we demonstrated that synthesized nanoscale polysaccharides efficiently targeted adipose-targeted macrophages,” Dobrucki says. “The surprise was—this was a big deal, actually—that, with this technique, we could deliver therapeutic agents aimed at adipose-derived macrophages with a very high efficiency. We found that 63 percent of the injected dose stayed within the adipose tissue for 24 hours. It was just remarkable. If you are planning to develop targeted treatment strategies, it is essential to maximize the retention of the drug within the area you are trying to target.”
Typically a standard, systemic approach with a medicine administered in the bloodstream would result in effective concentrations at the target area in the range of 1 percent or less. To have a concentration 63 times that is astonishing and was the highest concentration reported to date in the literature. Such targeting could lead to a need for smaller doses per treatment, and it could result in fewer, or less intense, side effects from the drugs themselves.
Swanson oversaw the team that prepared the mice population for the study and conducted blood marker and gene expression analyses. His group carefully monitored what the mice ate, ensuring that there was a control lean group, as well as the diet-induced obese population. An expert in nutrition and obesity, Swanson says that he and his fellow researchers hope these treatments can be a useful tool for lessening inflammation and improving disease prognosis. However, this would not be a replacement for a healthy lifestyle.
“The best way to control obesity and related diseases is a healthy diet and exercise,” Swanson says. “Controlling simple overeating is the biggest thing, but also eating healthy foods. For those who struggle to keep the weight off, nanomedicine-based therapeutics may soon help manage the disease.”
The study also resulted in collaboration among researchers on campus who might otherwise not interact on a single research project.
Swanson, for one, believes this was a benefit of the project, saying, “It’s been a great experience. This kind of collaboration has opened up my eyes and my research lab to a new area. We are very different—from an expertise perspective—but it merges well for a study like this. It has been truly mutually beneficial.”
The new therapy still needs additional testing before the procedure could be used in human subjects. Further pre-clinical studies are necessary to determine if there are any long-term toxicity issues with the procedure. Also, the injection within the body cavity itself poses some risks, so the research team also is investigating new ways to minimize the number of administrations in that area.
The potential benefits to humans are promising, according to the researchers. With this treatment, people who are trying to control obesity through diet and exercise would at least be able to reduce or eliminate potential obesity-related complications and could increase their ability to control obesity with greater safety.
A recent award from the National Institutes of Health of nearly $2 million, over the next five years, will allow the researchers from the U of I departments of bioengineering, animal sciences, molecular and integrative physiology, and veterinary pathology to continue exploring the use of this unique, tissue-specific drug delivery method that uses polysaccharides as nanoscale drug carriers, targeted at the inflammation-causing cells.
Initial funding for the work came from a Future Interdisciplinary Research Exploration (FIRE) seed grant from the College of Agricultural, Consumer and Environmental Sciences at U of I. The aim of the FIRE grant program is to spark creativity and collaboration between ACES faculty and their research partners, both within and outside of U of I.
“Efficient targeting of adipose tissue macrophages in obesity with polysaccharide nanocarriers,” is published in the journal ACS Nano. Authors include Liang Ma, Tzu-Wen Liu, Matthew A. Wallig, Iwona T. Dobrucki, Lawrence W. Dobrucki, Erik R. Nelson, Kelly S. Swanson, and Andrew W. Smith, all of the University of Illinois.
Adapted from a U of I Department of Bioengineering press release.