ReviewRemodelingtheTumorMicroenvironmentwithEmergingNanotherapeuticsQinChen,1,*GuangxuanLiu,1ShuoLiu,1HongyanSu,1YueWang,1JingyuLi,1andCongLuo2,*Thetumormicroenvironment(TME)hasprofoundimpactsoncancerprogres-sionandremodelingoftheTMEhasemergedasastrategytofacilitatecancertherapy.Recently,greatprogressinTMEmodulationhasbeenmade,espe-ciallywiththerapiddevelopmentsinnanomedicine.InthisreviewweoutlinethelatestadvancesinremodelingoftheTMEbasedonnanotherapeutics.First,novelstrategiesdevelopedtomodulatethetumorextracellularmatrix(ECM)arediscussed,includingdisruption,mimicking,andinterveningintumorECMfabrication.Then,emergingtumor-associatedfibroblast(TAF)-basednano-therapeuticsarereviewed,includingdisruptionandtargetingofTAFs.Further-more,recentdevelopmentsintumorvesseldisruptionandnormalizationarediscussed.Finally,emergingapproachesinresponsetotumorhypoxiaarepresented,withspecialemphasisondeliveringoxygen,generatingoxygen,andtargetingtumorhypoxia.TheTMEandNanotherapeuticsMalignanttumorsremainaworldwidethreattopublichealth.Althoughgreateffortshavebeenmadeinthedeliveryofdrugstosolidtumorsoverthepastfewdecades,theclinicaltherapeuticefficacyforcancerremainslimited[1].Intravenousinjectionisthemainstreamadministrationroutefordeliveryofantineoplasticagentsincancertherapy.However,deliveringanticanceragentstoanintracellulartargetsiteisalongtripfullofchallenges,suchasthesystemiccirculation,accumulationofthedrugintumorlesions,reachingdeeptumorpenetration,uptakebytumorcells,andintracellulardispositionofdrugs,andanyunconqueredstagemayresultinlimitedtherapeuticefficiency[2].Withfast-developingnanomedicine,anticancerdrugsloadedinnanoparticulatedrugdeliverysystems(nano-DDSs)readilyachieveprolongedsystemiccirculation,increasedaccumulationintumorviaanenhancedpermeabilityandretention(EPR)effect,improvedcellularuptake,andevencontrolleddrugreleaseintumorcells[3],whichisidealforanticancerdrugdelivery.However,thetherapeuticeffectsofcommerciallyavailablenanomedicineremainfarfromoptimal[4],sug...
