Platinum Drug Distribution in Cancer Cells and Tumors.pdf

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1、Chem.Rev.2009,109,4911–49204911PlatinumDrugDistributioninCancerCellsandTumorsAliceV.KleinandTrevorW.Hambley*SchoolofChemistry,TheUniversityofSydney,NSW2006,AustraliaReceivedMarch19,2009Contents1.Introduction49112.Cells49122.1.HowDoPlatinumDrugsEnterCells?49

2、122.2.WhatHappenstoPlatinumDrugsinthe4913IntracellularEnvironment?2.3.ActiveEffluxofPlatinumDrugs49132.4.MethodsforStudyingPlatinumDistributionin4914Cells2.4.1.Atom-BasedAnalyticalTechniques49142.4.2.Fluorescent-TaggedCompounds49152.4.3.FluorophoresasIndicat

3、orsofComplex4917Metabolism3.MulticellularInVitro3-DTumorModels4917AliceKleinobtainedherundergraduateChemistrydegreeattheUniversity4.Tumors4918ofSydneyin2008,completinganHonoursprojectonthesubjectof5.ConcludingRemarks4918platinumanticancercomplexes.Sheisnowu

4、ndertakingaPh.D.atthe6.References4918UniversityofSydneyandispursuingherinterestinplatinumchemistryunderthesupervisionofProfessorTrevorHambley.Inparticular,herresearchfocusesondevelopingnovelplatinum(IV)-intercalatorhybrid1.Introductioncomplexesandinvestigat

5、ingtheirpotentialasantitumouragentsincells.Theeraofplatinum-basedanticancerdrugswasheraldedbytheclinicalintroductionofcisplatin(1),asquare-planarplatinum(II)complexwhoseantitumorpropertieswerefirstreportedbyRosenbergin1969.1Thesuccessofcisplatinpavedthewayfo

6、rthesecond-andthird-generationplat-inum(II)drugs,carboplatin(2)andoxaliplatin(3),whiletheplatinum(IV)complexsatraplatin(4)hasrecentlyundergonephaseIIItrialsandwasconsideredforFDAapproval.2Platinumdrugscontinuetoplayacentralroleinthetreatmentofcancerandareus

7、edinthechemotherapeuticregimesofPublicationDate(Web):August28,2009

8、doi:10.1021/cr90010663,4aroundhalfofallcancerpatients.ThesearchfornewplatinumanticancerdrugsisdrivenbytheneedtoovercomeDownloadedbyUNIVSOUTHDAKOTAonOctober15,2009

9、http://pubs.acs.orgthesidee

10、ffectsandlimitedtumorpenetrationofexistingplatinumagents,aswellasintrinsicandacquiredresistance.Toachievesuchadvances,anunderstandingofthemecha-nismsbywhichtumorsandcellsdistributeandprocessTrevorHambl