Investigation of phototherapeutic effect of photosensitizer coated quantum dot nanoparticles on trichophyton rubrum

Onychomycosis, also known as tinea unguium is a fungal infection that affects the fingernails but is seen more commonly in the toenails. This infection can be caused by dermatophytes, yeasts, and molds. Dermatophytes are the most common cause of superficial fungal infections in our country and in the world. Trichophyton rubrum is the most common clinically encountered species among dermatophytes, which are divided into 3 main genres according to its causative agent and locality. Nail infections due to dermatophytes are more common in patients over 65 years of age, diabetics, and in immunocompromised patients. Oral antifungal use and topical medications are widely used in the treatment of these infections. The duration of antifungal treatment in dermatophytosis can be extended up to 12 months. However, clinical treatment failures are encountered in nail fungus infections due to the length of the treatment period and its frequent repetitions. There is a great need to develop a more effective and short-term method in the treatment of nail fungus infections. For this purpose, the use of various nanoparticles and local temperature increase (such as laser applications) separately or together is promising. In the treatment of cancer cells and infectious diseases, photodynamic treatment (PDT) is used which needs photosensitizers to be fully affected. There are current studies on PDT being used as an alternative and or supplement in some infectious diseases, cancers, and also dermatological disorders. Also, photothermal therapy (PTT) has been used for many medical treatments. For this, nanoparticles are used to kill the cell by light induced heating. In this study, the inhibitory effect of 5-Aminolevulinic acid (ALA) + Ag2S-GSH (QD) on T. rubrum alone and together with various laser applications was shown. ALA was used as the PDT agent, and the PDT application will be carried out in the safe laser range, and short-term (<5 minutes) photo stimulation. Ag2S-GSH quantum dots will be used as PTT agents. For this purpose, dual laser applications at more than one wavelength (640 and 808 nm) will be carried out in this experimental setup. In our study, only ALA and ALA +QDs (at concentrations of 0.1, 0.25, 0.5, and 1.0 mM) was not effective on planktonic T.rubrum cells without laser application. Similarly, partial effect of only ALA and ALA+QD combination on biofilm was determined. Without laser application, increasing concentrations of ALA alone (0.1, 0.25, 0.5, and 1.0 mM) exhibited 30%, 29.7%, 29.7%, and 39.3% inhibition, respectively, while at the same concentrations, QD was more effective when combined with ALA. ALA+QD showed high inhibition for all concentrations 0.1 mM, 0.25 mM, 0.5 mM, and 1.0 mM (51.3%, 39.8%, 49.9% and 54.2%) compared to only ALA. When laser application was added to the experimental setup, >99.9% inhibition was obtained for 0.25 mM, 0.5 mM, and 1.0 mM concentrations while 0.1 mM showed 99.97% and 89.3% inhibition. The whole experiment was repeated with only QD concentrations ranging from 0.1mM, 0.25 mM, 0.5 mM, and 1.0 mM and resulted in >99.9% inhibition with laser application. In conclusion, it was determined that nanoparticles (QD) caused an effective inhibition (>99.9%) on T.rubrum planktonic and biofilm cells with laser application. PTT applications can be seen as a promising application for dermatophyte treatment in the future.