A Near-Infrared-Triggered Mn,Fe-Doped Polyoxometalate Nanozyme Combined with Lactobacillus for the Chemodynamic/Photothermal Therapy of Candida Vaginitis

Vulvovaginal candidiasis (VVC) is a common fungal infection that significantly affects women's health worldwide. Antifungal agent therapies are not particularly effective for VVC and can further promote an imbalance in the vaginal microbiota, increasing recurrence. Nanozymes are currently being evaluated as an alternative therapy owing to their broad-spectrum antibacterial activity and negligible biological toxicity. However, their inherently low catalytic activity limits their antibacterial properties. In this study, an Mn,Fe-doped polyoxometalate (Mn,Fe-POM) nanozyme was successfully constructed as a potential treatment for VVC through the synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT). The developed approach was based on Lactobacillus in the vagina, which provides a suitable microenvironment for promoting the peroxidase (POD)-like activity of Mn,Fe-POM. Mn,Fe-POM-bound Lactobacillus exhibited excellent near-infrared-triggered POD-like activity for CDT and noteworthy photothermal performance for PTT. Electron transfer between Fe2+/Fe3+ and Mn3+/Mn4+ provided abundant active sites, increasing POD-like catalytic activity based on Fenton-like mechanisms and amplifying the CDT potential. In vitro, Mn,Fe-POM demonstrated a remarkable synergistic effect in killing Candida albicans (C. albicans) and disrupting the biofilm, while also preserving the Lactobacillus species. This outstanding anti-C. albicans activity was achieved without significant damage to the vaginal mucosa cells, reducing vaginal inflammation in an in vivo VVC mouse model. The increased Lactobacillus proportions and reduced C. albicans numbers allowed the reconstruction of healthy vaginal microbiota to decrease infection recurrence. This study presents an innovative and promising therapeutic approach for VVC.