A pH-responsive nanoplatform for delivery of curcumin and magnesium coordination driven nanozymes for colitis therapy

The treatment of inflammatory bowel disease (IBD) remains difficult because of the insufficient drug accumulation at lesion sites and the difficulty in regulating the complex reactive oxygen species (ROS) and hydrogen sulfide (H 2 S) microenvironment. Metal nanozymes, which have catalytic abilities similar to those of natural enzymes, provide a promising method for targeted drug delivery and therapeutic regulation. Therefore, in this research, a new oral nanoparticle drug delivery system was constructed. This system achieved targeted delivery and modulated ROS and H 2 S levels. In this system, curcumin (Cur) and magnesium (Mg) coordination driven nanozymes (C-M) were constructed, followed by encapsulation with chitosan, chondroitin sulfate, and alginate to create a C-M-encapsulated nanoparticle (C-M@aNP). C-M@aNP exhibited uniform particle size, strong stability in acidic environments, and pH-responsive characteristics, enabling effective scavenging of ROS and H 2 S. This nanosystem demonstrated excellent biocompatibility and facilitated CD44 receptor targeting, thereby promoting cellular uptake and endocytosis, which enhanced its anti-inflammatory functions. In a colitis mouse model, the C-M@aNP not only effectively regulated excessive levels of ROS and H 2 S in the inflamed colon but also reduced the expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and increased the expression of anti-inflammatory cytokines (TGF-β) while inhibiting the activity of proinflammatory enzymes (COX-2 and iNOS). In conclusion, C-M@aNP exhibits biological safety and significant therapeutic potential for IBD, suggesting its potential as a promising clinical treatment strategy. Download: Download high-res image (247KB) Download: Download full-size image