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Graduate Category:InterdisciplinaryTopic DegreeLevel:PhDinChemicalEngineering AbstractID#1010 BiologicalMechanismsInvolvedinNanoparticle-EnhancedRadiationTherapy AutumnParo1,2,Ilan Shanmugam1,3,RajivKumar1,3, AnnevandeVen1,3, ThomasJ.Webster2,and SrinivasSridhar1,3 1NanomedicineScienceandTechnologyCenter,2DepartmentofChemicalEngineering,3DepartmentofPhysicsNortheasternUniversity,Boston,MA02115 MetallicnanoparticlesemitAugerelectronsandphotoelectronsupon exposuretoX-rays.Whenselectivelydeliveredtotumors,these nanoparticlescanlocallyenhancetheeffectsofradiationtherapy. Previousinvitroworkhasprimarilystudiedtheeffectivenessof nanoparticle-enhancedtherapy,withoutelucidatingtheunderlying biologicalmechanisms1,2.Theobjectiveofthisprojectistodetermine whatbiologicalpathwaysareactivatedinirradiatedpancreaticcancercells pre-treatedwithgoldnanoparticles. Usingacombinationofclonogenic survivalassaysandWesternblotting,itwasdeterminedthatgold nanoparticlesenhancetheeffectsofradiationatclinicallyrelevantlevels viaupregulation ordownregulation ofspecificpathways. MTSandAlamar Bluecellviabilityassaysshowmildtoxicityuptoa doseof1mgofgoldnanoparticlesinCapan-1pancreaticcancercells v v v Externalbeamradiationisusedin60%of allcancerpatients Selectivelykillstumorcellsand minimizesdamagetohealthycells https://commons.wikimedia.org/wiki/File: Radium_radiotherapy_machine_1951.jpg v v UtilizesX-ray/metalinteractionsto enhanceradiationdose Goldisuseddueto: v Biocompatibility v Specificity v High-Z-edge v Highmassattenuation coefficient v Clonogenic cellsurvivalassayshowsGNP’senhancecelldeath atlowradiationdoses e- X-Rays e- NP e- (Gy) DNA Damage ROS H 2O eCell Death v v v Gray,Henry(1918).AnatomyoftheHumanBody. Philadelphia,Pennsylvania:LeaandFebiger https://commons.wikimedia.org/wiki/File:Gray1225.png Cancer.org predicts48,000 newcasesand40,000 deathsin2016 5yearsurvivalrateisonly 7% Currenttreatmentsinclude v Chemotherapy v RadiationTherapy v Surgery (Gy) v v Goldnanoparticlesup-regulatethe𝛾-H2AXproteinwhichisa DNAdamagemarkerlinearlycorrelatedtothenumberof doublestrandbreaks Goldnanoparticlesdown-regulateKras whichisaprotein involvedinregulatingthecellcycle. 1. J.F.Hainfeld,D.N.Slatkin andH.M.Smilowitz,Physicsinmedicineandbiology49(18), N309-N315(2004). 2. R.I.Berbeco,H.Korideck,W.Ngwa,R.Kumar,J.Patel,S.Sridhar,S.Johnson,B.D.Price,A. Kimmelman andG.M.Makrigiorgos,Radiationresearch178(6),604-608(2012). z SupportedbyNSFIGERTDGE- 0965843andHHS-CA188833-02