Table 1.

Target determinants for endothelial drug delivery.

Target determinant	Sub-cellular localization	Effect of pathology on target availability	Potential utility as target for drug delivery	References
PECAM-1	Cell–cell junctions in endothelial layer	Not usually affected	Prophylactic and therapeutic delivery to endothelium in lungs and other organs	9,13
ICAM-1	Tetraspanin microdomains at apical membrane	Upregulated in inflammation	Prophylactic and therapeutic delivery to vasculature in lungs and other organs, imaging of vascular pathology	10,14–17
VCAM-1	Tetraspanin microdomains at apical membrane	Upregulated in inflammation	Selective delivery to and imaging of inflamed endothelium in some organs	18–20
TM	Cell surface, single pass type I membrane protein	TM level can be suppressed in various pathological states	Cannot be used as a target	21–24
E-selectin	Cell surface, single pass type I membrane protein	Upregulated in inflammation	Selective delivery to and imaging of inflamed endothelium in some organs	25–27
P-selectin	Intracellular granules	Released upon inflammation	Selective delivery to and imaging of inflamed endothelium in some organs	28,29
Integrins αvβ3, αvβ5, α5β1	Cell surface	αvβ3 is upregulated in response to vascular damage, αvβ5 is upregulated by VEGF, TGF-a	Selective delivery to and imaging of tumor vasculature	30
ACE	Apical domains in plasmalemma	Suppressed in vascular pathology	Selective delivery to the pulmonary microvasculature	31–35
APP	Caveolae	Unknown	Delivery and imaging of caveolar pathways and trans-endothelial delivery	36–38
PV1 (Plvap)	Caveolae and fenestrae	Upregulated by VEGF	Delivery to caveolar pathways	38,39

PECAM-1, platelet-endothelial cell adhesion molecule 1; ICAM-1, intercellular cell adhesion molecule 1; VCAM-1, vascular cell adhesion molecule; TM, thrombomodulin; ACE, angiotensin-converting enzyme; APP, aminopeptidase P; PV1/Plvap, plasmalemma vesicle associated protein.