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Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

Arno, Maria C., Williams, Rebecca J., Bexis, Panagiotis, Pitto-Barry, Anaïs, Kirby, Nigel, Dove, Andrew P., O'Reilly, Rachel K.
Biomaterials 2018 v.180 pp. 184-192
antineoplastic agents, chemical bonding, composite polymers, glutathione, nanoparticles, physical properties, therapeutics, topology
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.