Supramolecular nanoarchitectonics of propionylated polyrotaxanes with bulky nitrobenzyl stoppers for light-triggered drug release

Abstract

Cyclodextrin (CD)-based polyrotaxanes (PRXs) are supramolecular polymers comprising multiple CDs mechanically interlocked onto a linear polymer chain by capping the polymer ends with bulky stoppers. Among various PRX derivatives, propionylated PRXs (Pr-PRXs) composed of propionylated α-CD and high molecular-weight poly(ethylene glycol) (PEG) form self-assembled nanoparticles in aqueous solution through hydrophobic interactions. Although Pr-PRX nanoparticles can encapsulate hydrophobic drugs in their hydrophobic domains, their release rate is limited. To improve the efficiency of drug release from Pr-PRX nanoparticles, ultraviolet (UV) light-dissociable Pr-PRXs were designed using 4,5-dimethoxy 2-nitrobenzyl groups as UV-cleavable bulky stopper molecules to facilitate UV-induced drug release. Photodegradable Pr-PRX (Pr-PD-PRX) was synthesized, and its UV-induced dissociation was examined. Pr-PD-PRX was completely dissociated via UV irradiation (365 nm) for 30 min. Additionally, Pr-PD-PRX nanoparticles encapsulating hydrophobic drugs collapsed upon UV irradiation, which promoted the release of the encapsulated drugs compared to non-degradable Pr-PRX nanoparticles. UV irradiation of drug-loaded Pr-PD-PRX nanoparticles resulted in higher cytotoxicity than non-irradiated Pr-PD-PRX and non-degradable Pr-PRX. Consequently, designing photodegradable PRX-based nanoparticles provides new insights into developing photoresponsive drug carriers and smart biomedical materials.