Healing Wounds With Nanoparticles

An experimental therapy developed by Einstein researchers has cut in half the time it takes to heal wounds compared to using no treatment at all. Details of the therapy, which was successfully tested in mice, were published in the Journal of Investigative Dermatology.

“Our nanoparticle therapy could be used to speed the healing of all sorts of wounds, including everyday cuts and burns, surgical incisions and chronic skin ulcers, which are a particular problem in the elderly and people with diabetes,” says study co-leader David J. Sharp, Ph.D., a professor of physiology & biophysics at Einstein.

Dr. Sharp and his colleagues had earlier discovered that an enzyme called fidgetin-like 2 (FL2) puts the brakes on skin cells as they migrate toward wounds to heal them. The researchers reasoned that the healing cells could reach their destination faster if their FL2 levels could be reduced. So they developed a drug that inactivates the gene that makes FL2 and then put the drug in tiny gel capsules called nanoparticles and applied the nanoparticles to wounds on mice. The treated wounds healed much faster than untreated wounds.

FL2 belongs to the fidgetin family of enzymes, which play various roles in cellular development and function. To learn more about FL2’s role in humans, Dr. Sharp suppressed FL2 activity in human cells in tissue culture. When those cells were placed on a standard wound assay (for measuring properties such as cell migration and proliferation), they moved unusually fast. “This suggested that if we could find a way to target FL2 in humans, we might have a new way to promote wound healing,” says Dr. Sharp.

At left: Microscopy image of normal mouse skin showing collagen deposits (red) and hair follicles (green). The other two images show healed mouse skin 14 days after being burned. Center: Untreated wound contains disorganized collagen and few hair follicles. Right: Wound treated to deplete fidgetin-like 2 levels resembles normal mouse skin.
At left: Microscopy image of normal mouse skin showing collagen deposits (red) and hair follicles (green). The other two images show healed mouse skin 14 days after being burned. Center: Untreated wound contains disorganized collagen and few hair follicles. Right: Wound treated to deplete fidgetin-like 2 levels resembles normal mouse skin.

Dr. Sharp and project co-leader Joshua D. Nosanchuk, M.D., a professor of medicine at Einstein and attending physician in infectious diseases at Montefiore, developed a wound-healing therapy that uses gene-silencing molecules called silencing RNA (siRNAs) that are specific for FL2. They bind to a gene’s messenger RNA (mRNA), preventing the mRNA from being translated into proteins (in this case, the enzyme FL2). However, “siRNAs on their own won’t be effectively taken up by cells, particularly inside a living organism,” says Dr. Sharp. “They will be quickly degraded unless put into some kind of delivery vehicle.”

To deliver siRNAs for curbing FL2, Dr. Sharp collaborated with Joel M. Friedman, M.D., Ph.D., a professor of physiology & biophysics and of medicine at Einstein, and study co-leader Adam Friedman, M.D., formerly director of dermatologic research at Einstein and Montefiore, who together had developed nanoparticles that protect molecules such as siRNA from being degraded as they ferry the molecules to their intended targets.

The nanoparticles with their siRNA cargoes were then tested by applying them topically to mice with either skin excisions or burns. In both cases, the wounds closed more than twice as fast as in untreated controls. “Not only did the cells move into the wounds faster, but they knew what to do when they got there,” says Dr. Sharp. “We saw normal, well-orchestrated regeneration of tissue, including hair follicles and the skin’s supportive collagen network.”