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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 14, 2015; 21(42): 12022-12041
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.12022
Table 1 Summary of studied targeted nanoparticles used in vitro/in vivo for drug delivery in hepatocellular carcinoma using different targeting moieties
Type of nanocarrierNPs compositionTargeted for receptorActive moietySpecific RemarksRef.
Synthetic or natural polymeric NPsPolyethylenglycol (PEG), dithiodipropionate, hyaluronic acidAsialogycoprotein receptor (ASGPR) , no receptor (EPR effect)Doxorubicin (DOX)The NPs were sensitive to acidic environment of endosomes and high intracellular Glutathion concentrations[62]
Synthetic or natural polymeric NPspoly(caprolactone), PEGno receptor (EPR effect)DocetaxelThe NPs had a long circulating characteristic and longer retention time in tumor cells[63]
Synthetic or natural polymeric NPsGalactose (GA), chitosan,ASGPR5-FU-[66,74,75]
Synthetic or natural polymeric NPsO-carboxymethyl chitosan, GAASGPRPaclitaxel (PTX)-[68]
Synthetic or natural polymeric NPsHyaluronic acid (HA), GAASGPRPTXThe dual targeting allows for the NPs to get internalized by tumor cells more specifically[69]
Synthetic or natural polymeric NPsHematoporphyrin, Bovine serum albumin (BSA)LDLDOXThe photosensitizing properties of hematoporphyrin allowed for an accurate monitoring of NP uptake by imaging[88]
Synthetic or natural polymeric NPsHeat-liable enterotoxin subunite B (LTB), BSAGanglioside GM1 receptor5-FU-[92]
Synthetic or natural polymeric NPsGalactosylated chitosan, polycaprolactoneASGPRCurcumin-[72]
Synthetic or natural polymeric NPsGalactosylated chitosan, mPEG-SHASGPRNorcantharidin (NCTD)The drug was actually loaded using ionic cross linkage between NCTD and chitosan[76]
Synthetic or natural polymeric NPsSM5-1, PLAMembrane antigens5-FU-[96]
Synthetic or natural polymeric NPsApotransferin, BSAtransferrin receptorDOX-[138]
Synthetic or natural polymeric NPsSynthetic or natural polymeric NPsApotransferrin, LactoferrinChitosan, retinoic acid (RA), AlbuminTransferrin receptorRA receptorDOXDOX--[139][105]
Mixed NPsGA, DOX, AlginateASGPRDOX-[70]
Mesoporous high surface area silica core fused to a liposome (protocell)Silica, PEG, Zwitterionic lipids, phosphatidylethanolamineSP94 receptor, no receptor (EPR effect)DOXThe fusogenic peptide used allows for more efficient internalization. The nanoporous silica core also gives the NPs, a significantly higher surface area[64]
Nano micellePEG, polycaprolactone, SPION, folateFolate receptorSorafenibThe SPION loaded NPs could be efficiently monitored using MR imaging[128]
Nano micelleRGD, PEG, stearic acid, chitosanIntegrinsDOX-[112]
Nano liposomeegg phosphatidylcholine, cholesterol, monomethoxy PEG-distearoyl phosphatidylethanolamine, and Lactose - dioleyl phosphatidylethanolamine (DOPE)ASGPRDOX-[73]
Nano liposomeAnti CD44 antibody, cholesterol, DOPE, DSPC, DSPE-(PEO)4-cRGDfK, DSPE-mPEGCD44DOX-[97]
Lipid nanocarriersLactobionic acid, Stearyl amine, lecithin, glyceryl monostearate, oleic acidAGPR5-FU-[71]
Magnetic NPsFeCl2, FeCl3, CMC, EpCAM aptamerEpithelial cell adhesion moleculeDOXThese magnetic nanoparticles were suggested as a candidate for MR imagine of HCC[113]
Magnetic NPsFe3O4/Fe, silicano receptor (EPR effect)ABT-888, TemozolamideThe co-delivery of the two drugs both inhibits transcription of survival genes and has cytotoxic effect[65]
BSA NPsGlycyrrhizic acid (GA), BSA, 10-hydroxycamptothecin (HCPT)ASGPRFITC-[67]
Gold NPGold, cetuximabEGFRgemcitabineWhen coupled with RF-hyperthermia, these NPs were significantly effective at tumor growth inhibition[94]
NanosuspensionDSPE, PEG, FA, soy lecithinFolate receptorDocetaxel-[136]
Dendrimerpoly(methacryloyl sulfadimethoxine) (PSD), PEG, LactoseASGPRDOX-[77]
Virus-like NPMS2 capsid, Ricin toxin A chain, SP94, H5WYG fusogenic peptide, PEGSP94 receptorDOX, cisplatin, 5-FU-[142]
Core-shell NPPoly(vinyl alcohol), albuminTransferrin receptorDOX, sorafenibThe synergistic effect of DOX and sorafenib here increased tumor inhibition more significantly[141]
MiscellaneousPLGA, PVA, chitosan, AsialofetuinASGPREPICo-delivery of EPI with tocotrienols as anti-oxidative agents, resulted in significantly lower cardiotoxicity and higher apoptosis level[85]
MiscellaneousBenzyl malolactonate, PEG, Fluorescein amine, Biotin, cyclic Biotin-RGD peptide, streptavidinBiotin Receptor, integrinsDOXThe use of streptavidin for grafting a peptide suggests that a number of peptides could be grafted in NPs without needing any additional chemistry[115]
Table 2 Summary of studied targeted nanoparticles used in vitro/in vivo for small interfering RNA delivery in hepatocellular carcinoma using different targeting moieties
Type of nanocarrierActive moietyTargeted receptorSuggested MechanismRef.
Lipid nanoparticleTetR siRNA--[31]
Novel nonocarrier consisting of a silica core fused to liposomes (called protocell)Model siRNASP94 protein and EPR-[64]
Galactose mediated trimethylchitosan cysteine NPsVEGF-siRNA and Survivin shRNA-expression pDNA (iSUR-pDNA)ASGPRSilencing of tumor growth genes[86]
A phospholipid-cholesterol nanocomplexPokemon siRNALDL receptorCell growth inhibition[89]
A SPION called SilenceMagHuman VEGF siRNAEGFRTumor growth inhibition[95]
PEGylated Polyethyleneamine SPIONSurvivin siRNAIntegrinInduction of apoptosis[114]
Virus-like nanoparticle of bacteriophage MS2Anti-cyclin siRNAFolic acid receptor, SP94, transferrin receptorInduction of apoptosis[142]
Lipid nanoparticleIntegrin b1 siRNAintegrinInhibition of proliferation and tumor cell death[116]