Targeted nanoparticle delivery provides boost for diabetes transplant

By Ian le Guillou, The Science Advisory Board contributing writer

January 20, 2022 -- Delivering immunosuppressant treatment via targeted nanoparticles could open the door to a long-lasting cure for type 1 diabetes. Transplanting insulin-producing cells is a promising approach to treat the disease; however, it is plagued by issues of immune rejection. In a new study, published January 17 in Nature Nanotechnology, mice treated with a reengineered therapy could tolerate a transplant for much longer with fewer side effects.

For the 1.6 million people in the U.S. living with type 1 diabetes, keeping the body's blood sugar levels within the right window at all times can be an ongoing challenge. Without the pancreas supplying insulin at the necessary time, individuals are forced to manually replicate the process using monitors, injections, and pumps every day.

One potential solution would be to replace the lost insulin-producing islet cells from the pancreas through transplantation. This would allow the body to produce its own insulin once more, offering a long-term cure for diabetes.

A key challenge is preventing the immune system from eventually attacking the new islet cells, leading to a relapse in the disease. This happens despite treatment with immunosuppressive drugs, such as rapamycin, which attempt to stop T cells from targeting the foreign tissue. These treatments are also plagued with side effects due to their impact on the immune system across the body.

"In the case of a transplant, you have to give enough rapamycin to systemically suppress T cells, which can have significant side effects like hair loss, mouth sores, and an overall weakened immune system," Evan Scott, PhD, co-senior author of the paper and an associate professor of biomedical engineering at Northwestern University, said in a statement.

Reducing these side effects and prolonging the lifespan of transplanted islet cells could allow transplantation to become a more common treatment for type 1 diabetes.

Retargeting an old drug

Scott and his colleagues set out to reengineer the immunosuppressive treatment so that it could more specifically target certain types of immune cells. They created nanoparticles that could carry molecules of rapamycin and deliver them to antigen-presenting cells in the lymph nodes, which help direct the T cells' activity.

The new treatment was tested in mice with diabetes that had received islet cell transplants. Mice that did not receive immunosuppressants rejected the new cells within 10 days, with a subsequent loss of blood sugar control. When the mice were given treatments every three days for two weeks, only 25% treated with standard rapamycin remained diabetes-free by the end of the study, 100 days after transplantation.

By contrast, 83% of mice treated with the nano-delivered rapamycin still had normal blood glucose concentrations by that time. The reengineered rapamycin also led to minimal side effects, and the mice had a stronger immune response than mice receiving the standard therapy.

"By changing the cell types that are targeted, we actually changed the way that immunosuppression was achieved," Scott said.

Importantly, the nanoparticles had to be administered through a subcutaneous injection compared to the typical oral delivery for rapamycin. This approach reduced the drug's metabolism in the liver, meaning that only half of the standard dose was necessary to be effective. Subcutaneous injections would be familiar to many people with type 1 diabetes, who inject insulin in this way without the need for a healthcare professional.

Working toward clinical use

Jacqueline Burke, the first author of the paper, was diagnosed with type 1 diabetes when she was nine. Burke previously worked on wound healing for diabetic foot ulcers. "As someone who's 26, I never really want to get there, so I felt like a better strategy would be to focus on how we can treat diabetes now in a more succinct way that mimics the natural occurrences of the pancreas in a nondiabetic person," she said.

These experiments provide an example of how engineered nanoparticles can change the mechanism of action for a drug by retargeting the cell types it acts on. Scott is patenting the method and is collaborating with industrial partners to test it in clinical trials.

"This approach can be applied to other transplanted tissues and organs, opening up new research areas and options for patients," said Guillermo Ameer, PhD, co-senior author of the paper and a professor of biomedical engineering at Northwestern University. "We are now working on taking these very exciting results one step closer to clinical use."

Do you have a unique perspective on your research related to diabetes or nanoparticles? Contact the editor today to learn more.

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