Enzyme‐Inspired Nanoreactor Containing Light‐Controlled “Trojan Horse” for Redox‐Hypersensitive Drug Delivery

Abstract

Abstract The applications of bioresponsive materials are limited by the low levels of physiological triggers and spatiotemporal barriers in vivo. To address these issues, a light‐controlled “Trojan horse” strategy is proposed by encapsulating a photo‐caged reducing agent within reduction‐responsive polymer vesicles. The polymersomes act as an enzyme‐inspired nanoreactor for efficient photo‐synthesis of dithiothreitol in situ, which attacks the disulfide bonds in polymer backbones and disintegrates the vehicles from the inside in a nanoconfined space. The assembly‐catalyzed photoreduction reaction overcomes the temporal and spatial barriers for hyper‐responsivity and enables ultrafast drug release even at 0.014 m m of dithiothreitol residues, a concentration 715 times lower than that required to cleave disulfide bonds. In addition, in both vitro and vivo, the equipment of upconverting nanoparticles and photothermal agents creates a near‐infrared light‐activated and self‐heating nanoreactor, which allows for efficient intracellular drug delivery and excellent photo‐chemo‐immunotherapy of tumors. This work presents a new approach to designing smart materials and a promising platform for on‐demand drug delivery applications.