In a new study, a multidisciplinary Mayo Clinic team discovered that nano-sized particles produced by cells in human fat have anti-inflammatory properties in immune cells and that the nanoparticles can carry drugs to boost that action. Nanoparticles are tiny objects that can be manufactured or derived from biological material; about 400 could fit on the width of a hair strand. Nanomedicine research seeks to understand how these particles' unique properties may be useful in treating disease.

"Everyone has fat. To be able to take something we all carry around and potentially use it to heal our bodies is a very exciting idea," says nanomedicine expert Joy Wolfram, Ph.D., who led the research, published in the journal Small.

Because inflammation plays a role in a variety of diseases including cancer and heart disease, the investigators hope their findings could eventually have beneficial implications for a broad range of conditions. However, they note that this research is still in early stages and not ready for patient use.

Tiny particles, enormous potential

In traditional drug delivery, medicine can be washed out of the body or end up in the wrong location before it has a chance to reach the disease site, such as a tumor. Instead, loading a drug into nanoparticles can protect it and guide it to the correct spot in the body, scientists say.

Nanoparticles from stem cells have already shown promise in providing therapeutic effects for inflammatory diseases. However, retrieving and processing nanoparticles from stem cells is expensive and time consuming. In contrast, nanoparticles from fat tissue are abundant and easy to access. They are also more efficient to process compared to stem cells – think hours, not months.  

Thus, the goal of this work was to determine whether nanoparticles produced by cells in fat tissue might share the anti-inflammatory properties of those derived from stem cells.

"Nanomedicine is one aspect of regenerative medicine, a field that's often seen as being synonymous with stem cells," says Shane Shapiro, M.D., study co-author and medical director of the Regenerative Medicine Therapeutics Suites at Mayo Clinic in Florida. "At Mayo, regenerative medicine is looking at the full breadth and depth of what's possible including and beyond stem cells. Using fat for this work is another piece of our effort to harness the human body's ability to be its own drug store — the ultimate goal of regenerative medicine."

Fat- vs. stem-cell nanoparticles: How do they stack up?

In the current study, the researchers took discarded, de-identified fat tissue from non-obese patients who had undergone liposuction for other purposes. Nanoparticles were collected directly from the fat tissue; the remaining tissue was processed and cultured for over a month to obtain nanoparticles from stem cells for comparison.  

The team then tested the ability of these nanoparticles to suppress inflammatory signals in human and animal immune cells. When they compared the anti-inflammatory effects of the fat-extracted nanoparticles to more traditional stem-cell-derived nanoparticles from the same patients, they were surprised to find the fat nanoparticles were just as effective.

To further examine the fat-derived nanoparticles, they loaded the particles with a common drug with anti-inflammatory effects. They not only found that the nanoparticles were capable of delivering medicine into cells, but also observed enhanced anti-inflammatory effects of the drug-loaded nanoparticles compared to the nanoparticles alone.

Because immune cells that promote inflammation are involved in many conditions, the scientists are hopeful that these fat-derived nanoparticles may eventually be useful in treating serious diseases that don't yet have effective therapeutic options.

Fat-derived nanoparticles will need to undergo further testing for consistency, safety, and effectiveness before they can be used in research on patients. "We still have a lot of work to do with respect to getting a treatment like this to patients," says Dr. Shapiro.

Meanwhile, Drs. Wolfram and Shapiro plan to work with Mayo colleagues on preclinical models of the use of these nanoparticles in treating cardiovascular, lung, and dermatological diseases.

This study received funding from Mayo Clinic's Center for Regenerative Medicine and other intramural sources. Partial support was also provided by the China Scholarship Council, Müller-Stiftung Mannheim and Vetter-Stiftung Mannheim, the Florida Department of Health Endowed Chair of Cancer Research, the Jack & Peggy Sturm Foundation, the U.S. Department of Defense, and the U.S. National Cancer Institute.

Other Mayo researchers are Ming Tian, M.D., the lead author of the study; Taylor Ticer; Qikun Wang, M.D.; Sierra Walker; Anthony Pham; Annie Suh, M.D.; Sara Busatto, Ph.D.; Rawan Alkharboosh; Laura Lewis-Tuffin, Ph.D.; Baoan Ji, M.D., Ph.D.; and Alfredo Quinones-Hinojosa, M.D.; with collaborators from Technion-Israel Institute of Technology and Heidelberg University in Germany.

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