Download Biological Mechanisms Involved in Nanoparticle-Enhanced Radiation Therapy Graduate Category: Interdisciplinary Topic Degree Level: PhD in Chemical Engineering

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).
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SupportedbyNSFIGERTDGE- 0965843andHHS-CA188833-02