Antifungal effect of titanium oxide nanoparticles on Candida glabrata internalized in human macrophages

María Elena Gómez-Hernández¹Shantal Lizbeth Baltierra-Uribe²Juan Castillo-Cruz²Ricardo Mondragon-Flores³GONZALEZ POZOS SIRENIA⁴Mónica Araceli Vidales-Hurtado^1*BLANCA ESTELA GARCIA-PEREZ^2*

• ¹Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada del IPN, Mexico City, Mexico
• ²Departamento de Microbiología, Instituto Politecnico Nacional, Mexico City, Mexico
• ³Departamento de Bioquímica, Cinvestav, Mexico City, Mexico
• ⁴Unidad de Microscopía Electrónica, LaNSE, Cinvestav, Mexico City, Mexico

Candida glabrata (Nakaseomyces glabrata) is an emergent human fungal opportunist pathogen. Recently, it was considered by the WHO as a fungal priority pathogen due to the high percentage of mortality (20-50%) from invasive candidiasis. This species shows high resistance to azoles, and in recent years, echinocandin resistance has been rising. Additionally, C. glabrata can evade immunological responses and manipulate macrophage activity to survive within these immune cells successfully. Titanium oxide (TiO2) is a photocatalytic material with recognized antimicrobial properties with and without photoactivation. This study aimed to investigate the antifungal effect of TiO2 nanoparticles on the planktonic form of C. glabrata and in internalized C. glabrata in macrophages. The nanoparticles synthetized are composed of a mixture of anatase and rutile phases with a quasi-spherical shape and a diameter range of 10-79 nm. These nanoparticles exhibit a significant effect on planktonic C. glabrata (approximately 90%) and a substantial reduction of fungal load (70-90%) in infected macrophages. Remarkably, the lower concentrations (1, 10, and 50 µg/mL) exhibited the best antifungal effect. Moreover, this impairment was associated with mechanisms independent of ROS production, since at those concentrations, there was no increase in ROS levels, and the antifungal effect was also observed in darkness. The induction of autophagy observed in cells treated with 50 µg/mL nanoparticles suggests that this process is a potential mechanism responsible for this activity. In conclusion, TiO2 nanoparticles exhibited a high antifungal effect on both planktonic and internalized yeasts, suggesting that autophagy may be involved. Together, the findings highlight the potential therapeutic use of TiO2 nanoparticles in the treatment of fungal infections.