(21d) Theranostic Nanoparticles for Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of disability and death in people under 45. Currently, there are no effective treatment options available for the approximately 10 million new cases each year worldwide. Damage caused by TBI occurs in two phases: (1) the primary insult, and (2) the secondary phase where damage can spread beyond the primary injury leading to severe neurocognitive, physical, and psychosocial impairment. We have developed image-guided, Gd-conjugated, oxygen reactive polymer (ORP) nanoparticles to reduce the reactive oxygen species (ROS)-dependent secondary phase of the injury. ORP has a high ROS sponge capacity and is able to protect cell cultures from ROS-mediated damage. Magnetic resonance imaging (MRI) revealed high uptake and retention or ORP in the damaged region of brain in controlled cortical impact mouse models of TBI, which was attributed to a passive targeting effect similar to the enhanced permeability and retention effect observed in tumors. Importantly, ORP significantly reduced neurodegeneration and gliosis surrounding the primary injury in these mouse models. ORP shows initial promise as an effective therapy for TBI and will help provide a better understanding of nanomaterial interaction with damaged brain.