ExtracellularVesiclesExtracellularvesiclesaremembranesurroundedstructuresreleasedbycellsinanevolutionarilyconservedmanner.Extracellularvesiclesroughlyfallintothesizerangesofviruses,bacteriaandplatelets.EVs—SizerangesCellMolLifeSci.2011Aug;68(16):2667-88EVs—CharacteristicsNatureReviews:drugdelivery,2013EVs—BiogenesisNatRevMolCellBiol.2018Apr;19(4):213-228.EVs—IntracellulartraffickingroutesNatRevMolCellBiol.2018Apr;19(4):213-228.EVs—UptakebyrecipientcellsNatureReviews:drugdelivery,2013NatRevMolCellBiol.2018Apr;19(4):213-228.EVs—ContentsCells.2019Feb12;8(2).Leukemia.2006Sep;20(9):1487-95.Epub2006Jul20.EVsmay(i)stimulatethetargetcellsdirectlybysurface-expressedligandsactingasakindof‘signalingcomplex’,(ii)transfersurfacereceptorsfromonecelltoanother,(iii)deliverproteins,mRNAandbioactivelipidsintothetargetcellsandfinally(iv)serveasavehicle(‘Trojanhorse’mechanism)totransferinfectiousparticles(e.g.,HIVorprions).EVs—IsolationHigh-ThroughputBulkMethodsNewEnrichmentMethodsMicrofluidicfilteringmethodsContact-freesortingofEVs.ImmunoaffinityEnrichment.EVs—PhysicalcharacterizationMicroscopy-BasedMethodsSEMTEMAFMcryo-TEMDynamicLightScatteringNanoparticleTrackingAnalysisTunableResistivePulseSensingWesternBlottingMethodsforthecharacterizationofextracellularvesiclesNatRevNephrol.2017Dec;13(12):731-749.Exosomesasbiomarkersofliverdiseases.EVs—BiomarkersEVsgeneratedbycancercellscontainavarietyofcargoJHepatol.2013Sep;59(3):621-5.SeminCellDevBiol.2017Jul;67:48-55.NeurodegenerativeproteinsfoundinexosomesandroleinmetalhomeostasisBiolCell.2015Nov;107(11):389-418.EnvironmentalToxicant-inducedExosomalReleaseandAssociatedDiseasePathogenesisToxicolSci.2017Jul1;158(1):3-13.Schematicrepresentationofhowrespiratoryexposure-inducedEVmaycontributetothepathogenesisofchronicdiseasesJToxicolEnvironHealthBCritRev.2018;21(3):142-160..AmodelfortheinvolvementofextracellularvesiclesintheintergenerationaltransmissionofenvironmentalstressorsEpigenomics.2015Oct;7(7):1165-71.EVs—ApplicationTrendsMolMed.2017Jul;23(7):636-650.EVsastherapeutictargets1Theendosomalsortingcomplexesrequiredfortransport(ESCRT)machineryismadeupofcytosolicproteincomplexes,knownasESCRT-0,ESCRT-I,ESCRT-II,andESCRT-III.Togetherwithanumberofaccessoryproteins,theseESCRTcomplexesenableauniquemodeofmembraneremodelingthatresultsinmembranesbending/buddingawayfromthecytoplasm.内吞体分选转运复合体(ESCRT)2EVsastherapeuticagentsChemRev.2018Feb28;118(4):1917-1950.3EVsasvehiclesfordrugdeliveryJCellMolMed.2018Feb;22(2):728-737ChemRev.2018Feb28;118(4):1917-1950.EurJPharmBiopharm.2017Oct;119:381-395.Advantagesandlimitationsofextracellularvesiclesfortherapeuticdelivery