Antimicrobial Photodynamic Therapy for Superficial, Skin, and Mucosal Fungal Infections: An Update

Abstract

The global burden of fungal infections is rising at an alarming rate, with superficial, cutaneous, and mucosal mycoses among the most prevalent. Conventional treatments rely on oral and topical antifungal agents; however, these therapies are often limited by adverse effects, toxicity, frequent recurrence, and poor patient adherence due to prolonged treatment regimens. Moreover, the emergence of antifungal resistance and multidrug-resistant species such as Candidozyma auris and Trichophyton indotineae highlights the urgent need for alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). aPDT is based on photophysical and photochemical processes involving a photosensitizer (PS), a light source, and molecular oxygen. When combined, these elements generate reactive oxygen species that selectively destroy microbial cells. In this review, we explore various PSs and their effectiveness in aPDT against infections caused by dermatophytes, Candida spp., and other pathogenic fungi. Promisingly, aPDT has demonstrated antifungal activity against both susceptible and resistant strains. In addition, aPDT has been successfully used in cases of mycoses unresponsive to conventional therapies, showing favorable clinical outcomes and overall safety. Current evidence supports aPDT as a valuable strategy for the management of cutaneous, mucosal, and superficial fungal infections and as a potential strategy to combat antifungal resistance.

Keywords: Candida spp.; antifungal; dermatophytes; mycoses; photodynamic therapy; photosensitizer.

Figure 1

Simplified Jablonski diagram illustrating the processes involved in photodynamic therapy (PDT). The process begins with the activation of the photosensitizer (PS) through irradiation using a light source with an appropriate wavelength. In its ground state (S₀), the PS absorbs light energy and transitions to an excited singlet state (S₁). From the S₁ state, the PS can either return to the S₀ state by emitting fluorescence or undergo intersystem crossing to the more stable triplet excited state (T₁). Once in the T₁ state, the PS may return to the S₀ state via phosphorescence or initiate photodynamic reactions by transferring excess energy to molecular oxygen. Two main reaction pathways can occur. The Type I reactions involve electron or hydrogen transfer from the excited PS to surrounding biomolecules, generating reactive oxygen species (ROS) such as superoxide anion (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radical (OH⁻). The Type II reactions involve direct energy transfer from the PS to molecular oxygen, producing singlet oxygen (¹O₂), a highly reactive species that causes oxidative damage to cellular structures.

Figure 2

Summary of the mechanisms of action of antimicrobial photodynamic therapy (aPDT) on fungal cells. aPDT acts on fungal cells by increasing the production of reactive oxygen species (ROS). When these ROS interact with the cell membrane and mitochondria, they can induce lipid peroxidation and reduce ergosterol content. In addition, ROS can lead to DNA damage, alter gene expression, impair the functionality of fungal antioxidant enzymes, and ultimately cause structural damage. Image created using Biorender (www.biorender.com, accessed on 27 May 2025).