Fig. 6.

Endothelial receptors for conjugate targeting in acute vascular pathology. Shown is a small vessel or capillary in cross-section, lined by endothelial cells (blue). Receptors (orange) are bound by drug conjugate (green circle) plus targeting moiety/ nanocarrier (green rectangle). Many receptors including PECAM and ICAM enable both intravascular and extravascular drug targeting. Factors that promote intracellular uptake (with retention of drug conjugate and recycling of receptor) include multivalent targeting moieties and low-flow state. Factors that modify uptake include ligand density, carrier geometry, and size. Ischemia/reperfusion injury (A) and acute vascular inflammation (B) both result in increased leukocyte recruitment and leaky tight junctions between endothelial cells. Treatment requires drug to be delivered intracellularly to the endothelium and to the interstitial space. Drug targeting to the specific receptors shown has resulted in treatment effect in animal models of these pathologies. (C) Shown is a blood clot within the lumen. Thrombosis and embolism both require the drug to remain in the vessel lumen to achieve direct therapeutic effect. Drug targeting to the receptors shown has resulted in treatment effect in animal models of thrombosis. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)