Delivering Nanoparticles Specifically to the Brain by Generating Artificial Brain Targets
Daniel Gonzalez-Carter, Molecular Bionics group at IBEC
Achieving efficient therapy delivery to the brain is one of the most pressing medical issues today. Therapy brain delivery is severely hampered by the protective blood-brain barrier (BBB), composed of the highly impermeable endothelial cells lining the brain vasculature. To overcome the BBB, therapies may be loaded onto nanoparticles functionalized with ligands which bind to target proteins expressed at the surface of brain endothelial cells (BEC), thereby increasing brain uptake. However, such strategies have inherent brain-specificity limitations, as the target proteins are also expressed on the vasculature of other organs, resulting in increased ‘off-target’ nanoparticle accumulation.
To achieve truly selective brain targeting, our group is developing a strategy to generate artificial targets exclusively at the BBB. This is done by exploiting the low endocytic rate of BEC, a key requirement for their high impermeability, to selectively retain exogenous targets on their surface. By generating nanoparticles capable of efficiently recognizing the artificial targets, we hope to increase nanoparticle delivery exclusively to the brain with minimal ‘off-target’ nanoparticle accumulation. Furthermore, we are developing an mRNA delivery platform to continuously re-generate the artificial targets from within the BEC to allow for repeated dosing in chronic diseases like Alzheimer’s disease.