Multivalent sulphur-modified biosilica nanostructures for bacterial enteritis therapy

Bacterial enteritis is a specific gastrointestinal tract disorder caused by pathogenic bacterial infection, which not only disrupts the commensal microbiota but also contributes to cascaded complications. Here, we prepared polyethyleneimine (PEI)-based mesoporous silica nanostructures, co-modified with -SH and -S-S- groups, to simultaneously eradicate the pathogenic bacteria, regulate the immune response, and reprogram the inflammatory microenvironment in the infected intestine. Referring to the multivalent sulfur modification, the -S-S- group, with its oxidizability, perturbs the glutathione balance within bacteria, while the combined reductive capacity of -SH and -S-S- scavenges excessive reactive oxygen species and mitigates inflammation-induced damage. Additionally, the well-developed nanopores with a positively charged PEI network facilitate the absorption of bacterial lipopolysaccharide, lipopeptides, flagella and cell-free DNA through hydrogen bonding and electrostatic interactions. Furthermore, the biosilica nanostructures enable the efficient encapsulation of conventional antibacterial agents, such as berberine chloride and norfloxacin, thereby achieving targeted delivery and reducing side effects, which represents a promising strategy for next-generation antimicrobial therapies.