A probiotic nanozyme hydrogel regulates vaginal microenvironment for Candida vaginitis therapy.

Molecular therapeutics are limited for Candida vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS2 nanozymes [reduced graphene oxide (rGO)] with Lactobacillus-produced lactic acid and H2O2, a responsive hyaluronic acid (HA) hydrogel rGO@FeS2/Lactobacillus@HA (FeLab) is developed. FeLab has simultaneous anti-Candida albicans and vaginal microbiota-modulating activities. In particular, the hydroxyl radical produced from rGO@FeS2 nanozymes and Lactobacillus kills C. albicans isolated from clinical specimens without affecting Lactobacillus. In mice with Candida vaginitis, FeLab has obvious anti-C. albicans activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of Firmicutes (especially Lactobacillus) and a decrease in Proteobacteria reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for Candida vaginitis therapy.