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1、AngewandteChemieAntitumorAgentsleukemias,malignantlymphomas,softtissueandbonesarcomas,andbreast,ovarian,prostate,bladder,gastric,andDOI:10.1002/anie.200602251bronchogeniccarcinomas.Thiswidelyusedoncologydrugisalsoassociatedwithdose-dependentcardiotoxicities,includ-AnAptamer–DoxorubicinP
2、hysicalConjugateasingdilatedcardiomyopathyandcongestiveheartfailure,aNovelTargetedDrug-DeliveryPlatform**whichmakethedevelopmentoftargetedDox-delivery[10]systemsofparticularimportance.Doxisknowntointer-VaishaliBagalkot,OmidC.Farokhzad,*RobertLanger,calatewithintheDNAstrandduetothepresen
3、ceofflatandSangyongJon*aromaticringsinthismolecule.Othercloselyassociateddrugs,suchasdonarubicin,havealsobeenshowntobe[11]intercalatedintoadoublehelixofDNA.SinceaptamersTheactivetargetingofdrugsinacell-,tissue-,ordisease-areknowntoformtertiaryconformationswithshortdouble-[12]specificman
4、nerrepresentsapotentiallypowerfultechnologystrandedregionsthroughintramolecularbasepairing,wewithwidespreadapplicationsinmedicine,includingthehypothesizedthatdoxorubicinmayintercalateintothesetreatmentofcancers.Inatypicalapproach,adrugandadouble-strandedregionsandformaphysicalcomplexwit
5、hligandarecomplementarilyfunctionalizedtoallowfortheaptamersthroughnoncovalentintercalation,aprocesscovalentornoncovalent(forexample,biotin–streptavidin)requiringnomodificationofthedrugortheaptamerconjugationfortargeteddelivery.Theresultingchemical(Figure1).Wepostulatedthattheresultinga
6、ptamer–Doxmodificationsofthedrugsand/ortheligandsmayadverselyaffectthesafetyandefficacyprofileofthedrugsandthebindingcharacteristicsoftheligands,therebyresultinginlessefficaciousdrug–ligandconjugates.Itwouldbedesirabletodevelopsimplebuteffectivetargeteddrug-deliverystrategiesthatdonotre
7、quirechemicalmodificationofthedrugortheligands.Recentlyourgroupandotherinvestigatorshaveusednucleicacidligandsoraptamersfortherapeuticanddiag-[1–6]nostictargeted-deliveryapplications.Aptamersarestruc-turedsingle-strandedDNAorRNAmoleculesthatcan[7][8]specificallybindtosmallmolec
