A Novel Targeted Nanoparticle for Traumatic Brain Injury Treatment: Combined Effect of ROS Depletion and Calcium Overload Inhibition

Survival after severe traumatic brain injury (TBI) depends on minimizing or avoiding secondary insults to the brain. Overproduction of reactive oxygen species (ROS) and Ca2+ influx at the damaged site are the key factors that cause secondary injury upon TBI. Herein, a TBI-targeted lipid covered radical scavenger nanoparticle is developed to deliver nimodipine (Np) (CL-PPS/Np), in order to inhibit Ca2+ influx in neurons by Np and to scavenge ROS in the brain trauma microenvironment by poly(propylene sulfide)(60) (PPS60) and thus prevent TBI-associated secondary injury. In post-TBI models, CL-PPS/Np effectively accumulates into the wound cavity and prolongs the time of systemic circulation of Np. CL-PPS/Np can markedly protect the integrity of blood-brain barrier, prevent brain edema, reduce cell death and inflammatory responses, and promote functional recovery after TBI. These findings may provide a new therapy for TBI to prevent the spread of the secondary injury.