Responsive polymers: a versatile platform for controlled drug delivery

Presenter: Dr Maria Chiara Arno

Polymeric nanoparticles are widely investigated to enhance the selectivity of therapeutics to targeted sites, as well as to increase circulation lifetime and water solubility of poorly soluble drugs. Among them, stimuli responsive nanoconstructs are particularly attractive for their ability to release their cargo in response to specific extracellular or intracellular stimuli. Using ring opening polymerization (ROP) and reversible-addition fragmentation chain-transfer (RAFT) polymerization techniques, we designed pH responsive and glutathione responsive polymers that can self-assemble in aqueous environment, and release the attached or encapsulated drug in response to an external trigger. A polymeric system with both pH-responsive acetal linkers and norbornene groups was designed to enable highly efficient post-polymerization modifications through a range of chemistries, to conjugate imaging agents and solubilizing arms to direct self-assembly.¹ The high cytocompatibility of the polymer and ability to be internalized by cancer cells allow this system to be used as a drug delivery vehicle upon conjugation of an anticancer drug. Furthermore, by investigating the topology change from cyclic to linear polymers, we studied the difference in self-assembly and particle stability between cyclic-linear graft and linear-linear graft copolymers. This difference 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, or via pH-triggered disassembly. This topological effect demonstrates the first example of topology-controlled particle disassembly for the controlled release of an anti-cancer drug in vitro.²

1. M. C. Arno, R. P. Brannigan, G. M. Policastro, M. L. Becker, and A. P. Dove. Biomacromolecules Article ASAP. DOI: 10.1021/acs.biomac.8b00744.

2.  M. C. Arno, R. J. Williams, P. Bexis, A. Pitto-Barry, N. Kirby, A. P. Dove, and R. K. O'Reilly, Biomaterials, Volume 180, 2018, Pages 184-192, DOI: 10.1016/j.biomaterials.2018.07.019.