Polyphenolic nanodot-integrated spindle nanoplatform heals oral mucositis via microbiota restoration and glycolysis inhibition

Oral mucositis (OM) is a debilitating complication occuring in most patients receiving chemotherapy. Through correlation analysis of oral microbiota sequencing data with host metabolomics data, we confirmed that disruption of the oral microbiota (dysbiosis) could lead to changes in metabolic activity in mucosal tissues, characterized by increased glycolysis in epithelial cells. Here, on the basis of the three-level microbiota-microenvironment-host metabolism regulatory network of in OM, we propose an integrated biofunctional nanoplatform (CP@ZS-NDs) that consists of a spindle-shaped zinc silicate core with polyphenol chlorogenic acid nanodots adsorbed on its outer surface, is delivered via a gel delivery system and has wet tissue surface adhesion and antioxidant capabilities. CP@ZS-NDs influence carbohydrate metabolism in host oral epithelial cells through regulation of the oral microenvironment by improving the microbiome composition. Moreover, we preliminary proved that CP@ZS-NDs promote the healing of OM by inhibiting the UDP-galactose-related metabolic pathway and regulating the Integrin α3β1-Fak-Rac1 axis. These findings demonstrate the effectiveness of CP@ZS-NDs in maintaining oral microbiota homeostasis, which is crucial for the treatment of OM and provide new insights for clinical treatment strategies.