Table 3.

Multiple strategies for a single target.

Target	Ligand	Carrier	siRNA target	Cell targets	Results of targeted ligand	Reference
Transferrin receptor	Transferrin	Liposome	RRM2	MV4-11, an AML line	Improved tumor accumulation (versus nontargeted NP) and enhanced silencing (versus control siRNA NP)	[54]
	T7 peptide	Liposome-polymer hybrid	EGFR	MCF-7	Marked tumor size reduction (versus nontargeted NP)	[134]
	Aptamer	SNALP liposome	GFP or LamA/C	HeLa-EGFP cells (in vitro)	Enhanced uptake and silencing (versus transferrin-NP)	[84]
	scFv1	scFv-polylysine conjugate	Survivin	U87 glioma cells	Enhanced silencing and improved survival of mice with orthotopic tumors (versus nontargeted NP)	[91]
	scFv	Liposome	(Fluorescently-labeled siRNA)3	Pancreatic, prostate, and melanoma cell lines	Specific delivery to orthotopic and metastatic tumors in vivo	[145]
CD44	HA	Liposome	PLK1	U87MG glioblastoma cells	Decrease PLK1 by 80%; prolonged survival in orthotopic model	[63]
	scFv	Polymer	KRAS	PANC-1, pancreatic cancer	Enhanced in vitro/in vivo silencing and efficacy (versus nontargeted NP)	[94]
	scFv	Polymer- (PEI-) iron oxide	Nontargeting siRNA	High (SGC-7901) versus low (A375) CD44 expressing cells	Increased uptake of targeted NP via magnetic resonance in SCC-7901 compared to A375	[146]
	Aptamer	Liposome	—	CD44+ (AS49, MDA-MB-231) versus CD44− (NIH/3T3) (in vitro)	Increased accumulation of targeted-NP in CD44+ cells	[147]
p32	Peptide (LyP-1)	Polymeric micelles	ID4	OVCAR-4, 8	Marked tumor reduction in vivo, administered IP	[10]
	scFv, trimerbody	—	—	MDA-MB-231	Widespread distribution of labeled antibody in tumor xenografts, particularly with the trimerbody	[148]
VEGFR2	VRBP1 peptide2	—	—	HUVEC, H460	VRBP1 reduced size of tumor xenografts	[149]
	Aptamer	Magnetic particle	—	PAEC, U87MG glioblastoma	Increased MRI signal in tumors in vivo (versus nontargeted NP)	[150]

¹scFv, single-chain variable fragment antibody; HA, hyaluronic acid; SNALP, stable nucleic acid lipid particles; PEI, polyethylenimine; RRM2, ribonucleoside-diphosphate reductase subunit M2; EGFR, epidermal growth factor receptor; GFP, green fluorescent protein; LamA/C, lamin A/C; PLK1, polo-like kinase 1; ID4, inhibitor of DNA binding 4; AML, acute myeloid cell leukemia; HUVEC, human umbilical vein endothelial cells; PAEC, porcine aortic endothelial cells; CPP, cell penetration peptide; NP, nanoparticle. ²Sequence of VRBP1 peptide - YDGNSFYEMVVGVKPASES; ³nontargeting siRNA.