Development of orally active gold nanozyme with multi-modalities for treatment of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic disease caused by multiple factors such as disrupted intestinal barrier functions, elevated levels of reactive oxygen species/reactive nitrogen species (ROS/RNS), and high-mobility group box 1 protein (HMGB1). These hazard signal molecules dysregulate mucosal immune responses, trigger inflammation, and then accelerate the severity of IBD. However, clinically commercialized medications are only focusing on the modulation of several cytokines in IBD. Therefore, to evaluate whether these hazard signal molecules are also involved in IBD, the mucoadhesive gold nanoparticle that acts as nanozyme (nanomaterial-based artificial enzyme) possessing superoxide dismutase (SOD) and catalase activity was exploited. Biocompatible glycol chitosan was used to introduce the mucoadhesive action to gold nanoparticle (denoted as glycol chitosan@AuNP). When glycol chitosan@AuNP was reacted with ROS/RNS-generating molecules, it could effectively convert ROS/RNS into water and oxygen molecules. Moreover, orally administered glycol chitosan@AuNP was successfully stayed at the mouse colon tissue. In addition, to show the synergetic effects in treating IBD, glycyrrhizin which can control HMGB1, was introduced to glycol chitosan@AuNP (denoted to Glycol chitosan-GL@AuNP). The orally treated glycol chitosan-GL@AuNP attenuated the inflammation on DSS (dextran sodium sulfate)-induced mice, which was confirmed by M2 polarization of macrophage at the laminar propria of colon tissue. Collectively, our findings suggested that mucoadhesive gold nanoparticle could be used as a potential therapeutic for IBD treatment.