Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

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 Version of Record

https://doi.org/10.1016/j.biomaterials.2018.07.019

Type

Article