A fall down the stairs, a car crash, a sports injury or an explosive blast can all cause traumatic brain injury (TBI). Patients often recover. But in the days or weeks following the hit, they can develop other serious, chronic conditions, such as depression and thinking and memory problems. Now scientists report in the journal ACS Nano a potential way to reduce these effects with a neuron-targeting nanoparticle, using an animal model of TBI.
When someone suffers from a head injury, the damage doesn't necessarily stop after the initial blow. The jolt can cause a cascade of after-effects - such as inflammation and ultimately the death of brain cells - and lead to physical and cognitive conditions that can continue for years. One promising approach to treating these after-effects involves delivering short stretches of RNA that can help shut down this chain reaction. But getting the RNA to the damaged part of the brain is a challenge because of the blood-brain barrier, which separates circulating blood from the fluid around brain cells. Sangeeta N. Bhatia and her colleagues at the Massachusetts Institute of Technology's Institute for Medical Engineering & Science wanted to see if they could rush therapeutic RNA to targeted brain cells soon after an injury while the blood-brain barrier is weakened.
The team, led by postdoctoral researcher Ester Kwon, engineered nanoparticles to target neurons by borrowing a protein from the rabies virus. They also loaded the particles with a strip of RNA designed to inhibit the production of a protein associated with neuronal cell death. When given to mice intravenously within a day of receiving a brain injury, the nanoparticles left the circulation and accumulated in the damaged tissue. Analysis also showed that the levels of the protein that the researchers were trying to reduce dropped by about 80 percent in the injured brain tissue.
The authors acknowledge funding from the Marie D. & Pierre Casimir-Lambert Fund, the David H. Koch Institute for Integrative Cancer Research at MIT, the National Cancer Institute, the National Institute of Environmental Health Sciences, the Defense Advanced Research Projects Agency and a Ruth L. Kirschstein National Research Service Award.
Article: Neuron-Targeted Nanoparticle for siRNA Delivery to Traumatic Brain Injuries, Ester J. Kwon, Matthew Skalak, Riana Lo Bu, and Sangeeta N. Bhatia, ACS Nano, doi: 10.1021/acsnano.6b03858, published online 18 July 2016.