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    Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

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    Pitto-Barry_Biomaterials.pdf (2.863Mb)
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    Publication date
    2018-10
    Author
    Arno, M.C.
    Williams, R.J.
    Bexis, P.
    Pitto-Barry, Anaïs
    Kirby, N.
    Dove, A.P.
    O'Reilly, R.K.
    Keyword
    Graft copolymers
    Cyclic polymers
    Disulfide linker
    Acetal linker
    Topology-controlled particle disassembly
    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.
    Peer-Reviewed
    Yes
    
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    Abstract
    The 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.
    URI
    http://hdl.handle.net/10454/17248
    Version
    Accepted manuscript
    Citation
    Arno MC, Williams RJ, Bexis P et al (2018) Exploiting topology-directed nanoparticle disassembly for triggered drug delivery. Biomaterials. 180: 184-192.
    Link to publisher’s version
    https://doi.org/10.1016/j.biomaterials.2018.07.019
    Type
    Article
    Collections
    Life Sciences Publications

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