Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of .

Phototherapy is an effective strategy to control () infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on . Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti- efficacy under near-infrared irradiation. In an intravaginal -infected murine model, treatment with the nanoplatform leads to a significantly decreased burden, particularly when leveraging candidalysin for further elevated phototherapy and inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical isolates. Overall, this biomimetic nanoplatform can target and bind with and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving infection with the power of enhancing phototherapy for improved anti- efficacy.