Biosilicification-mimicking chiral nanostructures for targeted treatment of inflammatory bowel disease

The cascade reaction of lipopolysaccharides (LPS), cell-free DNA (cfDNA), and reactive oxygen species (ROS), drives the development of inflammatory bowel disease (IBD). Herein, we construct polyethylenimide (PEI)-L/D-tartaric acid (L/D-TA) complexes templated mesoporous organosilica nanoparticles (MON) (PEI-L/D-TA@MON) by mimicking biosilicification under ambient conditions within seconds. The chiral nanomedicines include four functional moieties, wherein PEI electrostatically attracts cfDNA, tetrathulfide bonds reductively react with ROS, silanol groups adsorb LPS, and L/D-TA enables chiral recognition and inflammatory localization. Following oral administration, PEI-L-TA@MON exhibiting preferential conformation stereoscopically matches with mucosa and anchors onto inflammatory intestine for lesion targeting. PEI-L-TA@MON eliminates LPS, ROS, and cfDNA, alleviating oxidative stress, inhibiting inflammatory cascade, and maintaining immune homeostasis to achieve IBD therapy. In addition, the rapid synthesis, low cost, energy-free preparation, negligible toxicity, satisfactory therapeutic effect, and facile conversion on therapeutic modes of PEI-L-TA@MON will bring changes for IBD treatment, providing research values and translational clinical prospects. The cascade reaction of lipopolysaccharides (LPS), cell-free DNA (cfDNA), and reactive oxygen species (ROS), drives the development of inflammatory bowel disease (IBD). Here, Xu et. al. construct chiral nanomedicines composed of four functional moieties to eliminate LPS, ROS, and cfDNA for targeted treatment of IBD.