Abstract
Candida vaginitis, a prevalent inflammatory condition of the vagina attributable to infection with Candida albicans, afflicts a substantial proportion of women of childbearing age globally. Conventional clinical management predominantly relies on systemic or topical antifungal agents; however, these therapeutics exhibit limited efficacy against fungal biofilms and are prone to inducing antimicrobial resistance and increase the risk of recurrence. To address these limitations, we herein develop a hyaluronidase-responsive hyaluronic acid (HA) based hydrogel system, designated SiO2@FePt/Lactobacillus@HA (FePtLab). This multifunctional platform integrates peroxidase (POD)-mimicking SiO₂@FePt nanozymes with probiotic Lactobacillus strains. Crucially, the hydrogel remains inert under physiological conditions but undergoes selective enzymatic degradation upon exposure to hyaluronidase secreted specifically by Candida albicans, thereby enabling pathogen-triggered, spatiotemporally controlled release of its functional payloads. Locally released Lactobacillus restores and sustains an acidic vaginal microenvironment, competitively inhibits Candida overcolonization, and supplies endogenous H2O2 as a catalytic substrate. Concurrently, SiO2@FePt nanozymes harness this H2O2 to generate cytotoxic hydroxyl radicals (·OH), resulting in selective ablation of Candida albicans without collateral damage to commensal microbiota. By synergistically integrating stimulus-responsive delivery, dynamic microenvironment modulation, and targeted enzymatic antimicrobial action, the FePtLab system achieves potent, localized antifungal efficacy while preserving vaginal microbial homeostasis, offering a rationally engineered, safe, and sustainable therapeutic paradigm for recurrent and refractory candidal vaginitis.