Iodinated Near-Infrared Dyes as Effective Photosensitizers for the Photodynamic Eradication of Amphotericin B-Resistant Candida Pathogens

<b>Amphotericin:</b> B (<b>AmpB</b>)-resistant <i>Candida</i> (<i>C</i>.) species, such as <i>C</i>. <i>parapsilosis</i>, are among the most common causes of invasive fungal infections, posing significant challenges in hospital settings. Although <b>AmpB</b> is considered the first-line treatment owing to its broad-spectrum fungicidal activity, its use is hampered by severe side effects and the emergence of acquired resistance, particularly in <i>C</i>. <i>parapsilosis</i>, which exhibits reduced susceptibility to polyene, azole, and echinocandin-based antifungal drugs. Here, we present findings on photodynamic therapy (PDT) that targets the opportunistic fungal pathogens <i>C</i>. <i>parapsilosis</i> and <i>C</i>. <i>albicans</i> via the use of photosensitizers from the iodocyanine and newly developed iodinated Methylene blue families. These compounds contain heavy iodine atoms that increase the production of reactive oxygen species (ROS), the agents responsible for oxidative cellular damage, via the heavy-atom effect, which promotes intersystem crossing (ISC) and triplet-state formation. A strong antifungal effect was observed against <b>AmpB</b>-resistant <i>C</i>. <i>parapsilosis</i>, indicating a correlation between the quantum yield of ROS generation and the photosensitizing efficacy 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 <i>Candida</i> strains.