简介：Theadaptivetreatmenttolerance(ATT)ofcancercellsisthemainencumbrancetocancerchemotherapy.Apotentialsolutiontothisproblemistotreatcancercellswithmultipledrugsusingnanoparticles(NPs).Inthisstudy,wetestedtheco-administrationofcurcumin(Cur)anddoxorubicin(Dox)toMCF-7resistantbreastcancercellstoblocktheATTandelicitefficientcellkilling.Drugswereco-administeredtocellsbothsequentiallyandsimultaneously.Sequentialdrugco-administrationwascarriedoutbypre-treatingthecellswithalbuminnanoparticles(ANPs)loadedw让hCur(Cur@ANPs)followedbytreatmentwithDox-loadedANPs(Dox@ANPs).Simultaneousdrugco-administrationwascarriedoutbytreatingthecellswithANPsloadedwithboththedrugs(Cur/Dox@ANPs).Wefoundthatthesimultaneousdrugco-administrationledtoagreaterintra-cellularaccumulationofDoxandcellkillingwithrespecttothesequentialdrugco-administration.However;thesimultaneousdrugco-administrationledtoalowerintracellularaccumulationofCurwithrespecttothesequentialdrugco-administration.WeshowedthatthisresultwasduetotheaggregationandentrapmentofCurinthelysosomesassoonasitwasreleasedfromCur@ANPs,aphenomenoncalledlysosomotropism.Incontrast,thesimultaneousreleaseofDoxandCurfromCur/Dox@ANPsintothelysosomesledtolysosomalpHelevation,which,inturn,avoidedCuraggregation,ledtolysosomeswellinganddrugreleaseinthecytosol,andfinallyprovokedefficientcellkilling.Ourstudyshedthelightonthemolecularprocessesdrivingthetherapeuticeffectsofanti-cancerdrugsco-administeredtocancercellsindifferentmanners.

简介：ThispaperreportstheadsorptionofBovineSerumAlbumin(BSA)ontoDielectricBarrierDischarge(DBD)processedPoly(methylmethacrylate)(PMMA)surfacesbyaQuartzCrystalMicrobalancewithDissipationmonitoring(QCM-D)tech-nique.ThepurposeistostudytheinfluenceofDBDprocessingonthenatureandscaleofBSAadsorptiononPMMAsurfaceinvitro.ItwasobservedthatDBDprocessingimprovesthesurfacewettabilityofPMMAfilm,afactattributabletothechangesinsurfacechemistryandtopography.ExposureofthePMMAtoPhosphateBuffedSaline(PBS)solutionintheQCM-Dsystemresultedinsurfaceadsorptionwhichreachesanequilibriumafterabout30minutesforpristinePMMA,and90minutesforprocessedPMMAsurface.SubsequentinjectionofBSAinPBSindicatedthattheproteinisimmediatelyadsorbedontothePMMAsurface.ItwasrevealedthatadsorptionbehaviourofBSAonpristinePMMAdiffersfromthatonprocessedPMMAsurface.AsloweradsorptionkineticswasobservedforpristinePMMAsurface,whilstaquickadsorptionkineticsforprocessedPMMA.Moreover,thedissipationshiftofproteinadsorptionsuggestedthatBSAformsamorerigidstructureonpristinePMMAsurfacethatonprocessedsurface.ThesedatasuggestthatchangesinwettabilityandattendantchemicalpropertiesandsurfacetextureofthePMMAsurfacemayplayasignificantroleinBSAadsorptionprocess.