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

Abstract

Abstract 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.