Review Article

Targeted Delivery of siRNA Therapeutics to Malignant Tumors

Table 3

Multiple strategies for a single target.

TargetLigandCarriersiRNA targetCell targetsResults of targeted ligandReference

Transferrin receptorTransferrinLiposomeRRM2MV4-11, an AML lineImproved tumor accumulation (versus nontargeted NP) and enhanced silencing (versus control siRNA NP)[54]
T7 peptideLiposome-polymer hybridEGFRMCF-7Marked tumor size reduction (versus nontargeted NP)[134]
AptamerSNALP liposomeGFP or LamA/CHeLa-EGFP cells (in vitro)Enhanced uptake and silencing (versus transferrin-NP)[84]
scFv1scFv-polylysine conjugateSurvivinU87 glioma cellsEnhanced silencing and improved survival of mice with orthotopic tumors (versus nontargeted NP)[91]
scFvLiposome(Fluorescently-labeled siRNA)3Pancreatic, prostate, and melanoma cell linesSpecific delivery to orthotopic and metastatic tumors in vivo[145]

CD44HALiposomePLK1U87MG glioblastoma cellsDecrease PLK1 by 80%; prolonged survival in orthotopic model[63]
scFvPolymerKRASPANC-1, pancreatic cancerEnhanced in vitro/in vivo silencing and efficacy (versus nontargeted NP)[94]
scFvPolymer- (PEI-) iron oxideNontargeting siRNAHigh (SGC-7901) versus low (A375) CD44 expressing cellsIncreased uptake of targeted NP via magnetic resonance in SCC-7901 compared to A375[146]
AptamerLiposomeCD44+ (AS49, MDA-MB-231) versus CD44- (NIH/3T3) (in vitro)Increased accumulation of targeted-NP in CD44+ cells[147]

p32Peptide (LyP-1)Polymeric micellesID4OVCAR-4, 8Marked tumor reduction in vivo, administered IP[10]
scFv, trimerbodyMDA-MB-231Widespread distribution of labeled antibody in tumor xenografts, particularly with the trimerbody[148]

VEGFR2VRBP1 peptide2HUVEC, H460VRBP1 reduced size of tumor xenografts [149]
AptamerMagnetic particlePAEC, U87MG glioblastomaIncreased MRI signal in tumors in vivo (versus nontargeted NP) [150]

scFv, 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.