A probiotic nanozyme hydrogel regulates vaginal microenvironment for <i>Candida</i> vaginitis therapy.

Abstract

Molecular therapeutics are limited for <i>Candida</i> 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 <i>Lactobacillus</i>-produced lactic acid and H₂O₂, a responsive hyaluronic acid (HA) hydrogel rGO@FeS₂/<i>Lactobacillus</i>@HA (FeLab) is developed. FeLab has simultaneous anti-<i>Candida albicans</i> and vaginal microbiota-modulating activities. In particular, the hydroxyl radical produced from rGO@FeS₂ nanozymes and <i>Lactobacillus</i> kills <i>C. albicans</i> isolated from clinical specimens without affecting <i>Lactobacillus</i>. In mice with <i>Candida</i> vaginitis, FeLab has obvious anti-<i>C. albicans</i> activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of <i>Firmicutes</i> (especially <i>Lactobacillus</i>) and a decrease in <i>Proteobacteria</i> reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for <i>Candida</i> vaginitis therapy.