Nanomedicine: Can islet-targeting drugs nip diabetes in the bud?

Spherical nanoparticle (Fangting/Wikimedia Commons)

Recent research on Type 1 diabetes has begun focusing on prevention: Studies indicate that children start developing diabetes-related autoantibodies sometimes years before they develop clinical diabetes requiring insulin shots. The autoantibodies are an indicator of insulitis – a precursor condition in which the insulin-producing islets in the pancreas become inflamed and infiltrated with white blood cells.

In animal models, immune-suppressing drugs have been shown to blunt this attack by curbing the number of white blood cells circulating in the body. That reduces the need for insulin treatment – but at a high cost: Given systemically, the high doses needed to suppress the immune attack cause kidney toxicity, reduce the ability to fight infections, and decrease the body’s ability to respond to insulin.

That’s a tough sell for a child who doesn’t yet have symptoms of diabetes – but that’s where nanotechnology can help, say researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Children’s Hospital Boston. What if immunosuppressants could be delivered in far smaller doses, just to where they’re needed in the pancreas?

Researchers Don Ingber, director of the Wyss Institute and member of the Vascular Biology Program at Children’s, with Kaustabh Ghosh, now at the University of California, created minute, injectable particles (requiring an electron microscope to properly view) bearing the anti-inflammatory agent genistein. They tested the nanoparticles’ targeting ability by flowing them through a microfluidic device that mimics the dynamics of the bloodstream.

The microfluidic system used for testing. Drug-bearing nanoparticles were flowed through parallel channels lined with capillary endothelial cells from skin versus pancreatic islets.

One fluid channel was loaded with the type of endothelial cells that line blood capillaries in the skin. The other channel contained endothelial cells of a different type – those lining the capillaries near the pancreatic islets, the same cells to which white blood cells adhere before they launch their autoimmune attack.

The fluid-born particles had a 3-fold greater binding affinity to the islet capillary endothelial cells compared to the skin cells. The particles released their therapeutic payload of genistein over a period of 48 hours, and successfully prevented white blood cells from binding to the islet capillary cells.  (“Blanks” not loaded with drugs had no such effect.)

The researchers estimate that using nanomaterials, they can elicit the same immunosuppressive response as systemic treatment, but with a 200-fold lower drug concentration and little or no toxicity.

And there might be other uses: Ingber and Ghosh speculate that islet-targeting nanoparticles could incorporate imaging agents for early diagnostic screening and monitoring of pre-diabetic patients, or could be used to guide stem cells to the islets to help regenerate dying insulin-making cells.