Exploiting topology-directed nanoparticle disassembly for triggered drug delivery
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Publication date
2018-10Keyword
Graft copolymersCyclic polymers
Disulfide linker
Acetal linker
Topology-controlled particle disassembly
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© 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
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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.Version
Accepted manuscriptCitation
Arno MC, Williams RJ, Bexis P et al (2018) Exploiting topology-directed nanoparticle disassembly for triggered drug delivery. Biomaterials. 180: 184-192.Link to Version of Record
https://doi.org/10.1016/j.biomaterials.2018.07.019Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.biomaterials.2018.07.019