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dc.contributor.authorArno, M.C.
dc.contributor.authorWilliams, R.J.
dc.contributor.authorBexis, P.
dc.contributor.authorPitto-Barry, Anaïs
dc.contributor.authorKirby, N.
dc.contributor.authorDove, A.P.
dc.contributor.authorO'Reilly, R.K.
dc.date.accessioned2019-09-03T11:01:30Z
dc.date.accessioned2019-09-24T11:19:55Z
dc.date.available2019-09-03T11:01:30Z
dc.date.available2019-09-24T11:19:55Z
dc.date.issued2018-10
dc.identifier.citationArno MC, Williams RJ, Bexis P et al (2018) Exploiting topology-directed nanoparticle disassembly for triggered drug delivery. Biomaterials. 180: 184-192.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17248
dc.descriptionYesen_US
dc.description.abstractThe physical properties of cyclic and linear polymers are markedly different; however, there are few examples which exploit these differences in clinical applications. In this study, we demonstrate that self-assemblies comprised of cyclic-linear graft copolymers are significantly more stable than the equivalent linear-linear graft copolymer assemblies. This difference in stability can be exploited to allow for triggered disassembly by cleavage of just a single bond within the cyclic polymer backbone, via disulfide reduction, in the presence of intracellular levels of l-glutathione. This topological effect was exploited to demonstrate the first example of topology-controlled particle disassembly for the controlled release of an anti-cancer drug in vitro. This approach represents a markedly different strategy for controlled release from polymer nanoparticles and highlights for the first time that a change in polymer topology can be used as a trigger in the design of delivery vehicles. We propose such constructs, which demonstrate disassembly behavior upon a change in polymer topology, could find application in the targeted delivery of therapeutic agents.en_US
dc.description.sponsorshipERC are acknowledged for support to M.C.A., A.P.D. (grant number: 681559) and R.O.R. (grant number: 615142).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.biomaterials.2018.07.019en_US
dc.rights© 2018 Elsevier Ltd. All rights reserved. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en_US
dc.subjectGraft copolymersen_US
dc.subjectCyclic polymersen_US
dc.subjectDisulfide linkeren_US
dc.subjectAcetal linkeren_US
dc.subjectTopology-controlled particle disassemblyen_US
dc.titleExploiting topology-directed nanoparticle disassembly for triggered drug deliveryen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-07-10
dc.date.application2018-07-17
dc.typeArticleen_US
dc.type.versionAccepted manuscripten_US
dc.date.updated2019-09-03T10:01:33Z
refterms.dateFOA2019-09-24T11:22:54Z


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