Table 4.

Selected examples of “drug-free” NM targeting CAMs.

Class of targeting ligand	Targeting ligand	Targeted CAM	NM carrier	Implication/disease model	Reference
Carbohydrate	sLeX/sLea	E-selectin	Polyacrylamide (PAA)	Cell-free binding assays demonstrate a ~200 fold lower IC50 of NM compared to monovalent ligands	(133)
	sLeX/sLea (+tyrosine sulfate)	E-selectin (P-/L-selectin)	N-(hydroxyethyl)acrylamide	Ligand concentration dependent binding to E-selectin (and binding to P- and L-selectin) Inhibition of HL60 cell adhesion to E-selectin was increased	(134)
	sLeX/ galactose, fucose, sialic acid tyramine sulfate	E-, P- and L-selectin	HPMA	Multivalent presentation of sLeX-mimicking carbohydrates and sulfate groups effectively binds macrophages and reduces migration	(135)
	Mannose	P-selectin	PAA	Inhibition of neutrophil infiltration in rat peritoneal inflammation	(136)
	Sulfate groups	L-selectin	Dendritic polyglycerol	L-selectin and leukocyte rolling inhibition increase with size and degree of sulfation of dendritic polyglycerol sulfate	(137)
	Sulfate groups	P-/L-selectin	Dendritic polyglycerol	Reduced neutrophil infiltration in acute allergic contact dermatitis mouse model	(138)
	Sulfated β-lactose	L-selectin	Dendritic polyethylene oxide	Inhibition of neutrophil and macrophage infiltration in peritoneal inflammation in mice	(139)
	sLeX/ galactose, fucose, sialic acid tyramine sulfate	E-, P- and L-selectin	HPMA	Multivalent presentation of selectin-ligands effectively binds leukocytes and inhibits toxic liver injury	(140)
	Sulfate groups	P-/L-selectin	Dendritic polyglycerol	Decreased severity of disease in a murine model of polymyositis, reduced infiltration of pro-inflammatory T-cells	(141)
Peptide	E-selectin binding peptide DITWDQLWDLMK	E-selectin	HPMA	Inhibition of neutrophil adhesion under shear stress, reduction of alcohol-induced liver injury	(142)
	E-selectin binding peptide DITWDQLWDLMK	E-selectin	HPMA	Inhibition of high-fat diet promoted cardiac remodeling and reduction of atherosclerotic lesions in ApoE−/− mice	(87)
	IDLMQARGC IELLQARGC QITWAQLWNMMKGC	E-/P-selectin (L-selectin, ICAM-1)	Dermatan sulfate	Reduction of neutrophil arrest to endothelial cells and migration, reduced thrombus formation in deep vein thrombosis mouse model	(90, 143)
	Esbp DITWDQLWDLMK	E-selectin	HPMA	Prevention of B16-F10 melanoma lung metastasis	(86)
	CD44 binding peptide KRLVSYNGIIFFLR	CD44v3/CD44v6	HPMA	Prevention of 4T1 breast cancer lung metastasis	(144)
	ITDGEATDSG	ICAM-1	Poly-DL-lactic-co-glycolic acid	Blockade of DC and T-cell interaction, arrest of T-cell proliferation	(145)
Aptamer	Anti-VCAM-1 aptamer	VCAM-1	SPIONs	In vivo anti-tumor activity when combined with anti-IL-4Rα aptamer conjugated SPIONs	(131)