Abstract
However, in all the branched structures or dendrimersreported so far, each singledrughastobeindependentlycleavedtobereleased.Here,we report dendrimers thathavebeenbuilttocompletelyand rapidly dissociate intoseparate building blocksupon a single triggeringevent in the dendritic core.Thisprocessinducessimulta-neousreleaseofallend-groupmoleculesconnectedtothedendritictermini.Wetermthesemultiple-releasedendriticsystems“cascade-releasedendrim-ers”.Suchdendrimerscollapseintotheirseparatemonomericbuilding blocks after a single (chemical or biological)activation step that triggers a cascade of self-eliminationreactions, thereby releasing all the end groups from theperipheryofthe“exploding”cascade-releasedendrimer(seeSupportingInformation).Functionaldendrimersofthiskindmayfindapplicationinseveralfields.Oneparticularareais(targeted)drugdelivery,wherecascade-releasedendrimerspossesstwomajoradvan-tages over conventional dendrimers: 1)multiple covalentlybounddrugmoleculescanbesite-specificallyreleasedfromthetargetingmoietybyasinglecleavingstep;and2)theyareselectivelyaswellascompletelydegraded.Thus,incontrasttoconventionaldendrimers,theycanbeeasilydrainedfromthebody.Clearanceofmacromoleculesfromthebodymaybealimiting factor in current macromolecular drug-deliverysystems,
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