Single injection and multiple treatments: An injectable nanozyme hydrogel as AIEgen reservoir and release controller for efficient tumor therapy

Abstract

• AIEgens loaded thermo-sensitive hydrogel was used to achieve the goal of multiple intratumoral treatment with one injection. • Prussian blue nanoparticles were used to improve the hypoxic microenvironment of tumor. • Prussian blue nanoparticles enhance the therapeutic effect of AIEgen based PDT. Scheme 1. Schematic illustration of an injectable nanozyme hydrogel as AIEgen release controller for efficient tumor therapy. Direct intratumoral injection of aggregation-induced emission luminogen (AIEgen) enable direct photodynamic therapy (PDT) of tumors, but these injections may cause localized pain and a range of postoperative complications during frequent injections. In the present study, we developed a novel injectable nanozyme hydrogel that functions as AIEgens reservoir and release controller (ARC) and thereby facilitates more efficient tumor therapy. The ARC system was developed by simultaneously encapsulating Prussian blue (PB) nanoparticles and an AIEgen (CQu) in agarose hydrogels. PB converts near-infrared laser into heat, resulting in agarose degradation and consequent CQu release. Then PB nanozyme can drive the decomposition of endogenous hydrogen peroxide, then yielding oxygen (O 2 ) generation. Following subsequent low-power white light exposure, AIEgens can generate high levels of reactive oxygen species (ROS) with sufficient O 2 , thereby inducing tumor cell cytotoxicity. As hydrogels can persist within tumors for a minimum of 48 h, they can facilitate multiple rounds of treatment following a single injection. The present study is the first attempt to utilize hydrogel for AIEgens delivery, and the ARC system developed herein offers a novel means of supporting the clinical development of AIEgens treatment strategies for cancer patients.