Table 2.

Surface receptors for targeting specific endocytic pathways in vitro and in vivo. Abbreviations: AuNP, gold nanoparticle; LDL, low-density lipoprotein; MAL, maleimide; NP, nanoparticle; PEG, poly(ethylene glycol); PLA, polylactic acid; PLGA, poly(lactic-co-glycolic acid).

Surface receptor target	Targeting molecule	Pathway	Specificity	Nanoparticle examples	References
Annexin A1	mAnnA1	Caveolae	mAnnA1 is specific to Annexin A1 on caveolae of tumor endothelium in humans, rats, and mice, Annexin A1 is not prevalent in caveolae from healthy tissues	-Conjugated to AuNPs for targeting tumor endothelium in rats injected with 13 762 mammary adenocarcinoma cells	[122]
GP60	Albumin	Caveolae	GP60 is specific for albumin across the continuous endothelium	-Conjugated to polymer NPs for targeting BLMVECs -Conjugated to iron oxide NPs for targeting U87MG tumors in mice	[118,159,207,208]
Folate receptor alpha (FRα)	Folic acid	Caveolae	FRα is overexpressed in epithelial malignancies, has limited expression in healthy cells	-Conjugated to albumin NPs for targeting NIH:OVCAR3 cells	[119]
Aminopeptidase P (APP)	mAPP	Caveolae	APP is expressed in the endothelium of lungs, kidneys, and livers	-Conjugated to AuNPs for targeting the lung endothelium of athymic, nude mice	[121]
CD36—Scavenger receptor class B (SR-B)	A variety of ligands including LDLs and thrombospondin	Caveolae	CD36 is located on many types of cells past endothelial cells, such as macrophages and platelets, and binds to many different ligands	-Phosphatidylcholine conjugated to lipid NPs for targeting macrophages in C57BL/6 mice	[110,209]
CD204—Scavenger receptor class A (SR-A)	A variety of ligands including acetylated LDLs and lipopolysaccharide	Caveolae and clathrin	CD204 is located on many types of cells past endothelial cells such as macrophages and epithelial cells, and binds to many different ligands.	-Anti-CD204 conjugated to micelles for targeting macrophages in mice	[210–212]
LDL receptor family	A variety of ligands including LDLs and lactoferrin	Caveolae and clathrin	LDL receptors are located on many types of cells past endothelial cells such as macrophages and epithelial cells, overexpressed in liver tumors, and binds to many different ligands.	-Apolipoprotein-B lipid NPs for targeting HepG2 tumors in mice	[213–215]
Neonatal FC receptor	IgG FC, albumin	Clathrin	Neonatal FC receptor is specific to epithelial and endothelial cells in humans and mice	-Conjugated to PLA-PEG-MAL NPs for crossing the intestinal epithelium after oral administration in mice	[158,216,217]
Transferrin receptor	Transferrin	Clathrin	Highly expressed in solid tumor cells, as well as in blood brain barrier endothelial cells	-Conjugated to PLGA NPs for targeting brain capillary endothelial cells and astrocytes -Conjugated to AuNPs for targeting S.C. Neuro2A tumors in mice	[218–221]
Vascular cell adhesion molecule (VCAM-1)	Anti-VCAM-1	Clathrin	VCAM-1 is expressed on activated endothelial cells in tumors and during inflammation	-Conjugated to PEG-liposomes for targeting bEnd.3 cells and tumor vasculature in a CD1 nude, human Colo 677 xenograft mouse model	[104]
Epidermal growth factor receptor (EGFR)	Epidermal growth factor	Macropinocytosis	Present across many different cell types in the body, but is overexpressed in many tumor cell lines. EGFR also binds to many other types of growth factors	-Conjugated to AuNPs for targeting EMT-6 mammary carcinomas in mice	[222,223]
αV Integrins	iRGD	C-end rule (CendR)	Specific to αV integrins on tumor endothelium as well as angiogenic endothelium After binding to αV integrins, iRGD is cleaved in to CRDGK/R and then binds to neuropilin-1	-Conjugated to micelles for targeting 22Rv1, PC-3, PPC1, MIA PaCa-2, and BT474 tumors in mice	[143,144,224]