Microalgal-enhanced cerium oxide nanotherapeutics for alleviating inflammatory bowel disease via scavenging reactive oxygen species and modulating gut microbiota in colitis

Inflammatory bowel disease (IBD) poses significant therapeutic challenges due to its complex pathophysiology, which involves oxidative stress and dysbiosis of the intestinal microbiota. Antioxidant nanozymes offer promising intervention options because of their potent reactive oxygen species (ROS)-scavenging abilities; however, their instability and leakage in the upper gastrointestinal tract remain major challenges. This study introduced a novel oral drug delivery system, SP@CSC, which combines Spirulina platensis (SP), a natural microcarrier, with chitosan-functionalized cerium oxide (CSC) nanogels. The CSC nanogels demonstrated superior antioxidant capabilities compared to CeO2 nanoparticles. The acid-resistant and intestinal retention properties of SP improved the distribution and prolonged the residence time of CSC nanogels in the gut, thereby facilitating targeted antioxidant actions. SP@CSC effectively protected epithelial cells from oxidative stress-induced damage, restored mitochondrial function, and inhibited apoptosis. Additionally, SP@CSC exhibited immunomodulatory effects by suppressing macrophage infiltration and M1 polarization in IBD-associated microenvironments. In the dextran sulfate sodium-induced mouse colitis models, oral administration of SP@CSC alleviated IBD symptoms through restoring intestinal barrier integrity, modulating the immune-microenvironment, and enhancing the abundance and diversity of gut microbiota. These findings highlighted the potential of SP@CSC as a promising candidate for IBD treatment.