Title : In vitro assessment of silver nanoparticle–voriconazole combination against Aspergillus species and its mechanistic insights
Abstract:
Background: Aspergillus species are important opportunistic fungal pathogens associated with significant morbidity and mortality, particularly among immunocompromised individuals. The increasing emergence of antifungal resistance, particularly against azole antifungals, poses a major challenge to effective management of aspergillosis. Therefore, exploring alternative therapeutic approaches and combination strategies is essential to improve antifungal efficacy.
Objective: The present study aims to investigate the antifungal activity of silver nanoparticles (AgNPs), both alone and in combination with voriconazole, against clinically significant Aspergillus species and to elucidate the possible mechanisms responsible for their combined antifungal activity.
Methods: Aspergillus isolates obtained from clinical samples are being evaluated in the present study. AgNPs were synthesized using the Turkevich method and characterized using field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The antifungal activity of AgNPs and voriconazole is being determined using the broth microdilution method. The interaction between AgNPs and voriconazole is being evaluated using checkerboard assays and fractional inhibitory concentration indices (FICI). Selected isolates and treatment combinations are further being investigated using microscopic and molecular approaches to assess morphological alterations and changes in the expression of genes associated with fungal stress and antifungal response.
Results: Preliminary findings demonstrate measurable antifungal activity of AgNPs against Aspergillus isolates, with variation in susceptibility observed among species. Combination experiments are ongoing to determine the nature and extent of interaction between AgNPs and voriconazole. Mechanistic investigations, including microscopic and molecular analyses, are currently in progress.
Conclusion: This study is expected to provide insights into the potential of AgNPs as an adjunct to voriconazole therapy and may contribute to the development of alternative strategies for managing Aspergillus infections and addressing antifungal resistance.

