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简介：Inthisstudy,multiwalledcarbonnanotubes(MWCNTs)wereusedtoencapsulateamodelanticancerdrug,doxorubicin(Dox).Then,thedrug-loadedMWCNTs(Dox/MWCNTs)withanoptimizeddrugencapsulationpercentageweremixedwithpoly(lactide-co-glycolide)(PLGA)polymersolutionforsubsequentelectrospinningtoformdrug-loadedcompositenanofibrousmats.Thestructure,morphology,andmechanicalpropertiesoftheformedelectrospunDox/PLGA,MWCNTs/PLGA,andDox/MWCNTs/PLGAcompositenanofibrousmatswerecharacterizedusingscanningelectronmicroscopy(SEM),Fouriertransforminfraredspectroscopy,andtensiletesting.InvitroviabilityassayandSEMmorphologyobservationofmousefibroblastcellsculturedontotheMWCNTs/PLGAfibrousscaffoldsdemonstratethatthedevelopedMWCNTs/PLGAcompositenanofibersarecytocompatible.TheincorporationofDox-loadedMWCNTswithinthePLGAnanofibersisabletoimprovethemechanicaldurabilityandmaintainthethree-dimensionalstructureofthenanofibrousmats.Moreimportantly,ourresultsindicatethatthisdouble-containerdrugdeliverysystem(bothPLGApolymerandMWCNTsaredrugcarriers)isbeneficialtoavoidtheburstreleaseofthedrugandabletoreleasetheantitumordrugDoxinasustainedmannerfor42days.Thedevelopedcompositeelectrospunnanofibrousdrugdeliverysystemmaybeusedastherapeuticscaffoldmaterialsforpost-operativelocalchemotherapy.

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简介：BackgroundTheco-administrationofdexrazoxane(DEX)witheachdoseofdoxorubicin(Dox)isanefficientstrategytorelieveDox-inducedcardiotoxicity,however,themechanismsunderlyingthecardioprotectiveeffectofDEXhavenotbeenwellelucidated.MicroRNAs(miRNAs)areendogenous,smallnon-codingRNAsthatnegativelyregulategeneexpressionindiversebiologicalandpathologicalprocesses.TheaimofthepresentstudywastoinvestigatewhetherthecertaincardiacmiRNAswereinvolvedinDOX-inducedcardiotoxicity.MethodsMaleSDratswererandomizedintofivegroups,includingthe4-week(cumulativedose16mg/kg)andthe8-week(cumulativedose32mg/kg)Dox-treatedgroups,andthecorresponding4-weekand8-weekDoxplusDEX-treatedgroupsandthenormalcontrolgroup.Heartfunctionsoftheanimalsweredetectedbyechocardiography.Quantitativereal-timePCRwasusedtodeterminetheexpressionofcardiacremodeling,apoptosis-relatedgenesandmaturemicoRNAsofinterest.ResultsTheechocardiographydetectionshowedthatcardiacremodelingandimpairedheartfunctionwereobservedafter4-weekand8-weekDoxtreatment,andthecardiacremodelinganddecreasedejectionfraction(EF%)andfractionalshortening(FS%)wereefficientlyrescuedinthecorresponding4-weekand8-weekDoxplusDEX-treatedgroups.ThemyocardialexpressionofAnpandCTGFmRNAwassignificantlyupregulatedbyDoxtreatment,buttheupregulationofAnpandCTGFmRNAwasblockedintheDoxplusDEX-treatedgroups.IGF-1mRNAwassignificantlyup-regulatedinratmyocardiuminDoxplusDEX-treatedgroups,withnosignificantchangesofBcl-2andBAXmRNAexpression.MaturemiRNAsdeterminationdemonstratedthatthemyocardialmiR-1and-30eweresignificantlydownregulatedandmiR-21and-208bweresignificantlyup-regulatedinDoxtreatmentgroups,buttheabovemiRNAdysregulationcouldbeefficientlyreversedafterDEXtreatment.ConclusionsDEXcouldtunethemicroRNAsdysregulationinDox-treatedratmyocardium,miRNAsparticipatedinthecardioprotec

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简介：Gliomahasthehighestincidenceinthebraintumors.Thoughtreatedwithsurgicalresection,externalbeamradiationtherapy,andsystemicchemotherapy,patientswithgliomahavepoorprognosisbecauseofgliomarecurrence.

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.

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简介：AbstractBackground:High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB.Methods:Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.Results:The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.Conclusions:Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

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