Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a “Three-in-One” Strategy to Treat against Intravaginal Infection of <i>Candida albicans</i>

Abstract

Phototherapy is an effective strategy to control <i>Candida albicans</i> (<i>C. albicans</i>) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for <i>C. albicans</i> 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 <i>C. albicans</i> at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on <i>C. albicans</i>. 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-<i>C. albicans</i> efficacy under near-infrared irradiation. In an intravaginal <i>C. albicans</i>-infected murine model, treatment with the nanoplatform leads to a significantly decreased <i>C. albicans</i> burden, particularly when leveraging candidalysin for further elevated phototherapy and <i>C. albicans</i> inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical <i>C. albicans</i> isolates. Overall, this biomimetic nanoplatform can target and bind with <i>C. albicans</i> and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving <i>C. albicans</i> infection with the power of enhancing phototherapy for improved anti-<i>C. albicans</i> efficacy.