Endothelial cell and glycocalyx targeted nanoparticle drug delivery

The dysfunction of the glycocalyx in athero-prone regions in conjunction with the rising popularity of nano-scale therapeutics points to a possibility of a nanoparticle based glycocalyx treatment. The glycocalyx has a pore size cutoff of 7nm under healthy conditions, which become larger when its integrity is compromised. Also when the glycocalyx is shed there may be more receptors exposed to the bloodflow. By utilizing circulating nanoparticles we aim to target particles to specific regions undergoing atherogenesis to prevent further damage.  So far we have shown that the glycocalyx plays a role in 10nm sized polymer coated nanosphere uptake, visualized by fluorescently tagging components of the layer and particles.  Both collapse and degradation of glycocalyx led to significantly increased nanoparticles uptake with differences in localization within the cell monolayer.  Addition of degraded components to recover the glycocalyx showed a decrease in nanoparticle retention, suggesting the glycocalyx is responsible for the nanoparticle uptake and the permeability due to glycocalyx dysfunction can be undone.