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

Abstract

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

Cell Membrane-Coated Nanoparticles for Precision Medicine: A Comprehensive Review of Coating Techniques for Tissue-Specific Therapeutics

“…Dendritic cells were employed to promote tumor immune effects [100]. Vaginal endothelial cells were used to protect the cells from a toxin [71]. Neural stem cells were used to cross the bloodbrain barrier and specific targeting [72].…”

Enhanced Renal Carcinoma Treatment via Synergistic Photothermal/Photodynamic Therapy Using Hittorf's Phosphorus‐Decorated Polymeric Carbon Nitride Heterostructure

“…[11,12] However, the application of PTT may be limited by its side effects, such as hyperthermia-induced injury to healthy cells and tissues, while PDT can result in cytotoxic ROS that also cause damage to non-tumor cells. [13] To address these challenges, a contemporary approach has been proposed to synergistically combine PTT with PDT, thereby overcoming the individual limitations while still harnessing both therapies' benefits for tumor treatment. [14][15][16] The simplest approach to achieve synergistic performance in PDT and PTT involves the utilization of a single light absorber, followed by processing through the same light source and transmission system.…”

Multiphotonic Ablation and Electro-Capacitive Effects Exhibited by Candida albicans Biofilms

“…It has been demonstrated that phototherapy [8] and antimicrobial photodynamic therapy [9] are an effective strategy against C. albicans infection. Moreover, the assistance of optical nonlinearities promoted by femtosecond lasers seems to promise positive results; however, it is necessary to optimize the parameters of irradiation to improve the elimination of bacteria [10] and improve the quality of the photoinduced effects [11].…”