Folate-chitosan-gemcitabine core-shell nanoparticles targeted to pancreatic cancer

(整期优先)网络出版时间:2013-05-15
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Objective:Humanpancreaticcancerisoneofthemostcommonclinicalmalignancies.Theeffectofcomprehensivetreatmentbasedonsurgeryisgeneral.Theeffectsofchemotherapywerenotobviousmainlybecauseoflackoftargetingandchemoresistanceinpancreaticcancer.Thisstudyaimedtoinvestigatetheeffectsoffolatereceptor(FR)-mediatedgemcitabineFA-Chi-Gemnanoparticleswithacore-shellstructurebyelectrostaticsprayonpancreaticcancer.Methods:Inthisstudy,thelevelsofexpressionofFRinsixhumanpancreaticcancercelllineswerestudiedbyimmunohistochemicalanalysis.Theuptakerateofisothiocyanate-labeledFA-ChinanoparticlesinFRhighexpressioncelllineCOLO357wasassessedbyfluorescencemicroscopeandtheinhibitionrateofFAChi-GemnanoparticlesonCOLO357cellswasevaluatedbyMTTassay.Moreover,thebiodistributionofPEG-FA-ICGDER02-Chiintheorthotopicpancreatictumormodelwasobservedusingnear-infraredimagingandthehumanpancreaticcancerorthotopicxenograftsweretreatedwithdifferentnanoparticlesandnormalsalinecontrol.Results:TheexpressionofFRinCOLO357wasthehighestamongthesixpancreaticcancercelllines.TheFRmainlydistributedoncellmembraneandfewerinthecytoplasminpancreaticcancer.Moreover,theabsorptionrateoftheFA-Chi-GemnanoparticleswasmorethantheChinanoparticleswithoutFAmodified.TheproliferationofCOLO357wassignificantlyinhibitedbyFA-Chi-Gemnanoparticles.ThePEG-FAICGDER02-Chinanoparticleswereenrichedintumortissueinhumanpancreaticcancerxenografts,whilenon-targetednanoparticlesweremainlyinnormallivertissue.PEG-FA-Gem-Chisignificantlyinhibitedthegrowthofhumanpancreaticcancerxenografts(PEG-FA-Gem-Chivs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-ChinanoparticlesmightbeaneffectivetargeteddrugfortreatinghumanFR-positivepancreaticcancer.