Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

Maria C Arno, Rebecca J Williams, Panagiotis Bexis, Anaïs Pitto-Barry, Nigel Kirby, Andrew P Dove, Rachel K O'Reilly

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
162 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)184-192
Number of pages9
Early online date17 Jul 2018
Publication statusPublished - 1 Oct 2018


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