Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

Research output: Contribution to journalArticlepeer-review

Authors

  • Rebecca J Williams
  • Panagiotis Bexis
  • Anaïs Pitto-Barry
  • Nigel Kirby

Colleges, School and Institutes

External organisations

  • Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168, Australia.
  • Department of Chemistry, University of Warwick

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.

Details

Original languageEnglish
Pages (from-to)184-192
Number of pages9
JournalBiomaterials
Volume180
Early online date17 Jul 2018
Publication statusPublished - 1 Oct 2018