Chirality-Dependent Treatment of Ulcerative Colitis by Chiral Nanosheets

Chirality, an inherent property that is ubiquitous in nature, plays a vital role in biological processes. However, the impact of chiral materials on inflammatory diseases remains incompletely elucidated. Herein, chiral black phosphorus nanosheets (BP NSs), prepared through a chirality-transfer-assisted liquid exfoliation approach, exhibited chirality-dependent treatment efficiency of ulcerative colitis (UC). Benefiting from chirality-dependent cellular uptake via both clathrin- and caveolin-mediated endocytic pathways, L-BP NSs exhibited stronger cellular ROS scavenging than D-BP NSs. Upon oral administration, L-BP NSs exhibited superior intestine accumulation capability due to chiral nanosheet-mediated cascade targeting, that is, negatively charged L-BP NSs initially absorbed in the positively charged inflamed intestinal epithelium via electrostatic adsorption, followed by enhanced cellular uptake via chirality-dependent endocytosis. Meanwhile, L-BP NSs selectively enriched beneficial bacteria (e.g., Lactobacillus ) and suppressed harmful ones (e.g., Proteobacteria ), leading to a gut microbiota balance. In the delayed therapeutic UC model, the L-BP NSs group achieved an average colon length of 8.24 cm, longer than those of the D-BP NS (7.16 cm) and DL-BP NS (7.60 cm) groups. This study opens an avenue for the application of chiral BP NSs in UC and provides a chirality-dependent target treatment strategy for inflammatory diseases.