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Protein Delivered with Gold Nanoparticles Helps Fix Muscle Injuries

Gold particles

(Sharon McCutcheon, Unsplash)

2 Oct. 2018. A bioengineering lab at Harvard University devised a technique using gold nanoscale particles to deliver a protein to reduce inflammation from muscle injuries in lab mice. A description of the technique and results of the preclinical tests appear in yesterday’s issue of Proceedings of the National Academy of Sciences (paid subscription required).

The team of Harvard bioengineering professor David Mooney and doctoral student Theresa Raimondo is seeking a better process to deliver protein therapies, where proteins in their natural state do not work reliably or for any length of time. An example is Interleukin-4, a type of protein known as a cytokine, produced by the immune system. In this case, the immune system generates Interleukin-4 to control inflammation, a condition that often accompanies muscle tears and similar injuries.

But Interleukin-4 delivered externally does not stay active in the body for any length of time, which requires large doses that can have unwanted adverse effects. Mooney’s lab at Harvard’s Wyss Institute, a biological engineering research center, studies drug delivery technologies, including materials that deliver therapies harnessing the immune system. As reported in March in Science & Enterprise, these drug-delivery methods are being investigated for cancer immunotherapies. Raimondo, the lead researcher in this study, attached Interleukin-4 to gold nanoparticles, making it possible to deliver the protein directly to the injury, allowing the protein to accumulate at the injury site to work for longer periods without large repeated doses.

The Interleukin-4 nanoparticles interact with a type of white blood cell in the immune system known as macrophages that are formed from precursor cells called monocytes. When tissue damage, infection, or foreign substances appear, monocytes transform into macrophages to become the first line of defense against these disruptions. When tissue damage occurs, macrophages first respond by promoting inflammation, but later reverse course to reduce inflammation and encourage tissue repair and growth.

Raimondo and Mooney tested their hypothesis that Interleukin-4 delivered with gold nanoparticles would cause macrophages to switch from a pro- to anti-inflammatory state. They first assessed Interleukin-4 nanoparticles with human cells in lab cultures and found the Interleukin-4 interacted with macrophages to become more anti-inflammatory. The researchers then injected gold Interleukin-4 nanoparticles into lab mice induced with leg muscle injuries.

The results show Interleukin-4 from the gold nanoparticles accumulates at the injury site, and after 15 days, the treated mice develop more muscle fiber than untreated mice. Moreover, the leg muscles in the injured mice receiving gold Interleukin-4 nanoparticles contract with more force than similar mice receiving free-floating Interleukin-4.

“By exploiting the inflammatory response,”says Raimondo in a Wyss Institute statement, “this technology may significantly improve the therapeutic and functional outcomes of existing treatments that focus on the direct regeneration of muscle.” The team plans to extend this technique to treating inherited and progressive muscle diseases, such as Duchenne muscular dystrophy.

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