Treating and Protecting against Recurrent Vulvovaginal Candidiasis Using the Vaginal Epithelial Cell Membrane-Based Photoimmunotherapeutic Nanoplatform

Recurrent vulvovaginal candidiasis (RVVC) is an opportunistic infection predominantly caused by Candida albicans ( C. albicans ) and is particularly prevalent among individuals on immunosuppressants. Currently, there are no FDA-approved therapies for specifically controlling RVVC, mainly due to the need for therapeutics against RVVC that require both antifungal treatments to resolve active infections and strategies to prevent recurrence. This study introduces a biomimetic photoimmunotherapeutic nanoplatform consisting of an adjuvant-encapsulated polymeric core stabilized by a photosensitizer-loaded vaginal epithelial cell membrane coating to treat and protect against RVVC. With its cell membrane camouflaging, the nanoplatforms target and enhance adherence to the intravaginal site of C. albicans infection, allowing the nanoplatform to resist being flushed away by vaginal fluids. Upon subsequent near-infrared irradiation, the nanoplatform's targeted photothermal power effectively eliminates C. albicans while minimizing thermal damage to surrounding healthy tissue. Postphotothermal treatment, the generated C. albicans -based debris and candidalysin-captured nanoplatform (serving as a nanotoxoid), along with adjuvant, are processed by resident antigen-presenting cells to promote multiantigenic immunity. This response provides protection against secondary intravaginal C. albicans infection (RVVC model) and C. albicans -induced systemic infection even under immunosuppressive conditions (septicemia model). Notably, anti- C. albicans antibodies produced in the pretreated mice exhibit comparable affinity to clinically isolated C. albicans strains, indicating potential for clinical application. Overall, this study underscores the potential of the proposed photoimmunotherapeutic nanoplatform for the effective treatment and prevention of RVVC.