Glycan-Modified Cellular Nanosponges for Enhanced Treatment of Cholera Toxin-Induced Secretory Diarrhea

Cholera is a severe infectious disease caused by the Gram-negative bacterium <i>Vibrio cholerae</i> after colonization in the intestinal tract. Cholera toxin (CT), a key exotoxin protein, primarily causes acute secretory diarrhea and life-threatening complications in infected patients. Traditional approaches remain insufficient for effectively treating cholera, underscoring the need for innovative countermeasures to eliminate CT-caused symptoms. Here, we report a glycan-modified cellular nanosponge for the enhanced treatment of CT-induced secretory diarrhea. Specifically, intestinal epithelial cell membrane-camouflaged nanosponges are functionalized with a glycan receptor to promote their capability for CT neutralization, thereby competitively inhibiting CT entry into host cells. Moreover, an inhibitor is encapsulated into the cellular nanosponge to synergistically improve the therapeutic effect of diarrhea by blocking the excessive chloride ion efflux from the cystic fibrosis transmembrane conductance regulator (a crucial anion channel) on the membrane of CT-intoxicated epithelial cells. Upon oral administration, the biomimetic nanomedicine effectively eliminates CT-induced secretory diarrhea and intestinal injuries in mice. Overall, this study highlights the potential of glycan-modified cellular nanosponges as promising and broad-spectrum therapeutic agents against secretory diarrhea caused by bacterial exotoxins.