Rabies Virus‐Inspired Metal–Organic Frameworks (MOFs) for Targeted Imaging and Chemotherapy of Gliom

MOFDrug-DeliverySystemsRabiesVirus-InspiredMetal–OrganicFrameworks(MOFs)forTargetedImagingandChemotherapyofGliomaChaoqiangQiao+,RuiliZhang+,YongdongWang+,QianJia+,XiaofeiWang,ZuoYang,TengfeiXue,RenchuanJi,XiufangCuiundZhongliangWang*Abstract:Theblood–brainbarrier(BBB)restrictsaccesstothebrainofmorethan98%oftherapeuticagentsandislargelyresponsiblefortreatmentfailureofglioblastomamultiforme(GBM).Therefore,itisofgreatimportancetodevelopasafeandefficientstrategyformoreeffectivedrugdeliveryacrosstheBBBintothebrain.Inspiredbytheextraordinarycapabilityofrabiesvirus(RABV)toenterthecentralnervoussystem,wereportthedevelopmentandevaluationofthemetal–organicframework-basednanocarrierMILB@LR,whichcloselymimickedboththebullet-shapestructureandsurfacefunctionsofnaturalRABV.MILB@LRbenefitedfromamorecompre-hensiveRABV-mimicstrategythanmimickingindividualfeaturesofRABVandexhibitedsignificantlyenhancedBBBpenetrationandbraintumortargeting.MILB@LRalsodisplayedsuperiorinhibitionoftumorgrowthwhenloadedwithoxaliplatin.TheresultsdemonstratedthatMILB@LRmaybevaluableforGBMtargetingandtreatment.IntroductionGlioblastomamultiforme(GBM)isahighlyaggressivebraintumorwithalowsurvivalrate,poorprognosis,andhighriskofrecurrence.[1]AlthoughextensiveeffortshavebeendevotedtothedevelopmentofnumerousantitumoragentsfortreatingGBM,therapeuticefficacyremainslimitedandtreatmentsareoftenineffective.[2]Theseshortcomingsareprimarilyduetothepresenceoftheblood–brainbarrier(BBB),whichactsasabarrierwithhighlyselectiveperme-abi