Macrophage-biomimetic liposomes delivery of carbon dots nanozymes ameliorate ulcerative colitis by modulating inflammation pathways and remodeling the redox microenvironment

Abstract

As a recurrent chronic inflammatory intestinal disease, ulcerative colitis (UC) has seriously affected the life quality of patients. Numerous studies have demonstrated excessive reactive oxygen species (ROS) are involved in the occurrence and development of UC, and manipulating ROS expression in the intestinal microenvironment to lower the redox signaling and oxidative stress is a promising strategy in UC therapeutics. We previously demonstrated that carbon-dots (C-dots) nanozymes with superoxide dismutase-like activity could effectively clear ROS and alleviate inflammation, while the accurate lesion location targeting is still a crucial factor in impacting their therapeutic efficiency. In this study, inspired by naturally occurring intercellular interactions, macrophage cell membrane-coated liposomes were constructed to deliver C-dots to amplify their efficiency. The obtained C-dots@Lipo-M endowed C-dots with prolonged circulation time and inflammation targeting capability. In addition, this delivery platform could be co-localized with mitochondria where ROS generated. In dextran sulfate sodium (DSS)-induced UC models, C-dots@Lipo-M exerted satisfactory preventive and therapeutic effects on colitis by reversing the shortened colon length, scavenging ROS, decreasing the expression of pro-inflammatory cytokines, and reducing barrier protein expression at colon sites. Further transcriptome sequencing revealed that C-dots@Lipo-M might alleviate intestinal inflammation by modulating inflammation pathways and remodeling the redox microenvironment. Collectively, this study provides a new targeted strategy to improve nanozymes therapeutic efficiency and extends their biomedical applications on inflammation-related diseases.