Photodynamic therapy for pathogenic fungi

Abstract

Photodynamic therapy (PDT) is a minimally invasive approach, in which a photosensitiser compound is activated by exposure to visible light. The activation of the sensitiser drug results in several chemical reactions, such as the production of oxygen reactive species and other reactive molecules, whose presence in the biological site leads to the damage of target cells. Although PDT has been primarily developed to combat cancerous lesions, this therapy can be employed for the treatment of several conditions, including infectious diseases. A wide range of microorganisms, including Gram positive and Gram negative bacteria, viruses, protozoa and fungi have demonstrated susceptibility to antimicrobial photodynamic therapy. This treatment might consist of an alternative to the management of fungal infections. Antifungal photodynamic therapy has been successfully employed against Candida albicans and other Candida species and also against dermatophytes. The strain-dependent antifungal effect and the influence of the biological medium are important issues to be considered. Besides, the choice of photosensitiser to be employed in PDT should consider the characteristics of the fungi and the medium to be treated, as well as the depth of penetration of light into the skin. In the present review, the state-of-the-art of antifungal PDT is discussed and the photosensitiser characteristics are analysed.

Photoinactivation of Candida albicans using methylene blue as photosensitizer

“…Several studies that evaluated azole-resistant Candida species, noted that these strains were sensitive to PDT [11][12][19][20] . The photosensitizer and light application specifically on the site affected by candidiasis, dramatically reduces the local and systemic side effects, allowing the photodynamic therapy to be seen as a promising treatment against Candida albicans 21 .…”

“…It is used with different purposes in microbiology and pharmacology for quite some time and, lately, has been applied on PDT as a photosensitizing drug in association with a continuous light source. So that the photosensitizer can be one light-activated by laser, the light applied must present a specific wavelength 6,20 . In this study, the red light with a wavelength of 660 nm was used, corresponding to the absorption spectrum of methylene blue, and was adjusted to the appliance before illumination.…”

“…The most important factor governing the PDT results is how the FS interacts with the cells in the tissue or target lesion, and the key aspect of this interaction is related to the FS intracellular location. The incubation time is required to allow the drug to be absorbed by the microorganism and accumulate in the cell structures 20 , such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membrane 3 . During irradiation, it is necessary that FS is already located inside the cell, because the singlet oxygen, formed after light application, presents minimal diffusion (100nm) and cytotoxic effect only in the place where it is produced 15 .…”

The influence of photodynamic therapy parameters on the inactivation ofCandidaspp:in vitroandin vivostudies

“…Target cells must be first exposed to PS for a specific period of time, known as pre-irradiation time (PIT), before illumination. PDT results in reactive oxygen species (ROS), which promote cell damage and death [9][10][11]. The development of microbial resistance to such therapy seems to be improbable, since the mechanism of action involves multiple targets and ROS are non-specific agents.…”

Blue Dye and Red Light, a Dynamic Combination for Prophylaxis and Treatment of Cutaneous Candida albicans Infections in Mice

“…Numerous published studies have shown PDT to be highly effective in the in vitro inactivation of fungi (19,20,31). In addition, it is considered that the development of resistance to PDT by microbes is an unlikely event, because PDT is typically a multitarget process, which is a difference between PDT and most other antifungal drugs (22).…”