简介:Overthepastdecades,cellsurfacecharge,althoughexperimentallyobserved,hasnotbeenwellunderstoodparticularlyfromtheviewpointofbiophysics.Ourrecentstudieshaveshownthatallcancercellsexhib让negativesurfacechargesthataredirectlyproportionaltothesecretedlacticacid,auniquecancermetaboliccharacteristic:highrateofglycolysis.Wehavethereforedesignedanddevelopedasetofelectrically-charged,fluorescent,andsuper-paramagneticnanoprobes,capableofsensitivedetectionofcancercellsbasedonthesurfacecharges.Theseprobesareutilizedtobindontocellsviaelectrostaticreactionforcaptureandmagneticseparation.Inthisfashion,weareabletocharacterizecellsurfacechargesthatareregulatedbydifferentmetabolicpatterns,thereforeeffectivelydistinguishingthecancercellsfromthenormalcells.All22cancercellsofdifferentorgansarefoundtobenegativelychargedthereforeboundstronglybythepositively-chargednanoprobes,whereasthenormalcellsshowinsignificantbindingtothenanoprobesofeitherchargesigns(positiveornegative).Thisfindingsuggeststhatalltestedcancercellsarenegatively-chargedandnormalcellsareeithercharge-neutralorslightlypositive.Fordiagnosis,cancercellscanbedetected,electrostaticallybound,andmagneticallyseparatedinbloodbychargedandsuper-paramagneticnanoprobes.Intherapeutics,circulatingcancercells(CTCs)canbefilteredandremovedinacontinuousfashiontoreducetheriskofcancermetastasis.Ifsuccessful,thisnewnanotechnologywillrevolutionizeearlycancerdiagnosisandpotentiallyenablenewtherapeuticsinclinicalsettings.
简介:近日,来自中科院生化所和复旦大学的研究人员在国际学术期刊cancercell在线发表了一项最新研究进展。LKB1基因能够编码丝氨酸/苏氨酸蛋白激酶LKB1,研究发现该激酶可以调节细胞能量代谢、抑制生长增殖和维持细胞极性,而这些都是该基因抑制肿瘤的重要机制。虽然LKB1能够调节细胞生长和能量代谢,但在非小细胞肺癌中,LKB1失活如何协调肿瘤进展与代谢之间的关系仍未可知。在该项研究中,研究人员利用KrasG12D;Lkb1lox/lox小鼠模型进行了相关研究,发现在肺部恶性腺瘤和鳞状细胞癌中,活性氧(ROS)水平存在差异。
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:Integrinανβ6isexpressedatanundetectablelevelinnormaltissues,butisremarkablyupregulatedduringmanypathologicalprocesses,especiallyincancerandfibrosis.Noninvasiveimagingofintegrinανβ6expressionusingaradiotracerwithfavorableinvivopharmacokineticswouldfacilitatediseasediagnosisandtherapymonitoring.Throughdisulfide-cyclizedmethod,wesynthesizedinthisstudy,anewintegrinανβ6-targetedcyclicpeptide(denotedascHK),andradiolabeleditwith99mTc.Theabilityoftheresultingradiotracer99mTc-HYNIC-cHKtodetectintegrinανβ6expressioninpancreaticcancerxenograffsandidiopathicpulmonaryfibrosiswasevaluatedusingsmall-animalsingle-photonemissioncomputedtomography(SPECT)/computedtomography(CT).99mTc-HYNIC-cHKshowedsignificantlyimprovedinvivometabolicstabilitycomparedtothelinearpeptide-basedradiotracer99mTc-HYNICHK.99mTc-HYNIC-cHKexhibitedsimilarbiodistributionpropertiesto99mTc-HYNIC-HK,butthetumorto-muscleratiowassignificantlyincreased(2.99±0.87vs.1.82±0.27,P<0.05).High-contrastimagesofintegrinανβ6-positivetumorsandbleomycin-inducedfibroticlungswereobtainedbySPECT/CTimagingusing99mTc-HYNIC-cHK.Overall,ourstudiesdemonstratethat99mTc-HYNIC-cHKisapromisingSPECTradiotracerforthenoninya-siveimagingofintegrinανβ6inlivingsubjects.