Review Article

Targeted Delivery of siRNA Therapeutics to Malignant Tumors

Table 1

Ligands targeting endothelial and tumor cells.

Ligand/target1CarriersiRNA and/or active moietyCellsResultsOther commentsReferences

cRGD2/v3/5Polymer (PEI)3siVEGFR2N2A neuroblastoma allografts, implanted SC Marked inhibition of tumor growth (versus nontargeted NP) May target physiologic angiogenesis
[22]
Blocked copolymers micellessiVEGF/siVEGFR2HeLa
xenografts, SC
Marked inhibition of tumor growthSilencing both VEGFR2/VEGF more effective than either alone[27]

APRPG/VEGFR-1Polymer (PEI) siVEGFMCF7 xenografts, SC  Targeted and nontargeted PEG-NP inhibited tumor similarlyReduction of intratumoral VEGF and mRNA greater with targeted NP[34] 
Liposomesi-mTORB16F10, IV, tumor-laden lungsTargeted and nontargeted NP reduced tumor burden similarlyWild-type PTEN expressing tumors[35]

cNGR/CD13Liposomesic-MYC/doxorubicinHT-1080 (fibrosarcoma) xenografts, SCTumor uptake and inhibition greater with targeted NPHT-1080, a CD13+ cell[38]

F3/nucleolin  Silk-polylysine-copolymer NPPlasmid-based luciferase expressionMDA-MB-231 
xenografts, SC
Targeted NP increased gene expression in tumors Only study in vivo with F3 ligand; F3 more effective than CGKRK in vitro[44] 
LiposomessiPLK1PC3
(in vitro study)
Uptake and silencing greater with targeted therapyCells pretreated with siPLK1 were more sensitive to the inhibitory effects of paclitaxel[42]

CGKRK/p32NanowormsMitochondria-targeting peptideOrthotopic breast cancer model (MCF10CA1a)Targeted NP gave greater tumor inhibition than nontargeted NPAddition of iRGD increased tumor inhibition of targeted NP[45]

iRGDPEI micellesShsurvivin/paclitaxelA549 lung cancer 
xenografts, SC
Greater tumor size inhibition with targeted therapyPlasmid-based expression of shRNA; dose-response inhibition; no siRNA studies yet[51]

Selected representatives of targeted nanoparticles. 2See text for amino acid sequences of ligands; 3PEI, polyethylenimine; NP, nanoparticle; siVEGFR2, small inhibitory RNA targeting VEGFR2; PLK1, polo-like kinase 1; SC, subcutaneous; shRNA, small hairpin RNA expressed by plasmids; siRNA, small inhibitory RNA.