Figure 2.

Possible mechanisms of nanostructure extravasation. In the case of a continuous vascular endothelial barrier, nanostructures may be internalized by endothelial cells, e.g., via caveolae, transported via trans-cellular transport mechanisms and escape into the extracellular space via exocytosis. It is generally accepted that extravasation through tight gap junctions is limited to molecules or particles smaller than 10 nm.³³,¹¹² In the case of tumor vasculature, nanostructures may also escape the vasculature via transendothelial channels (TEC) and fenestrae. Molecules or particles up to 100 nm diameter may escape the vasculature via this route.¹ Where the vasculature is sinusoidal/discontinuous (e.g., liver, spleen), nanostructures and large molecules may readily escape the vasculature.