When treating neurological diseases, the up-take, penetration, and cellular interaction of a therapeutic within the brain is critical to the success of the therapeutic. However, there is a knowledge gap in knowing how changes to the extracellular matrix (ECM), brain edema, glial cell function, and blood-brain barrier disruption affect the diffusion, interactions, and cellular uptake of therapeutics following injury to the brain. Our research combines nanotechnology, data science, imaging, and neuroscience tools with preclinical models to understand and quantify transport limitations at the macro- and micro-scale in the brain, which can guide therapeutic design and implementation. When engineered nanoparticles leverage transport behavior in the brain, these platforms can be targeted to regions of the brain that contain diseased cells, as well as to specific cell types within those regions, resulting in improved neuroprotection and attenuation of neuroinflammation in brain injury models.

In this seminar, we will focus on the use of nanotherapeutics for neuroprotection in brain injury in newborns and children, who have unique physiologies compared to adults and are underserved by therapeutic technology development. We focus specifically on engineering therapeutics that mitigate or attenuate ongoing injury in the brain, with the goal of improving neurological function and quality of life across the lifespan. As part of this work, we have developed living brain tissue models that are tunable to different stimuli and that capture the regional complexity and variability in response to injury and treatment. In this talk, I will discuss our use of whole hemisphere brain slices to evaluate cellular-extracellular changes in the brain microenvironment and screen therapeutics, including nanotherapeutics. I will show key design considerations that increase nanoparticle uptake and transport within the brain for improved neuroprotection in neonatal and pediatric brain diseases.