Title : Iodinated near-infrared dyes as effective photosensitizers for the photodynamic eradication of Amphotericin B-resistant Candida pathogens
Abstract:
Amphotericin B (AmpB)- resistant Candida (C.) species, such as C. parapsilosis, are among the most common causes of invasive fungal infections and pose significant challenges in hospital settings. AmpB is considered the first-line treatment for severe fungal infections due to its broad-spectrum fungicidal activity. However, despite its efficacy, treatment is associated with severe side effects and the development of acquired resistance, particularly in C. parapsilosis, which has also shown reduced susceptibility to polyenes, azoles, and echinocandins. Here we present findings on photodynamic therapy (PDT) targeting the opportunistic fungal pathogens C. albicans and C. parapsilosis using photosensitizers from the iodo-cyanine and iodo-methylene blue families. These compounds contain heavy iodine atoms that enhance the production of reactive oxygen species (ROS), the agents responsible for oxidative cellular damage. Iodination improves photosensitizer efficacy through the heavy-atom effect, promoting intersystem crossing (ISC) and triplet-state formation, which leads to increased ROS production. A strong killing effect was observed against AmpB-resistant C. parapsilosis, indicating a correlation between the quantum yield of ROS generation and the antifungal efficacy of the photosensitizers under near-infrared (NIR) light irradiation. The combination of efficient cellular uptake and enhanced ROS generation positions iodinated photosensitizers as promising candidates for the treatment of drug-resistant Candida strains.
