Fungicidal efficacy of green-synthesized organosolv lignin-capped silver-based nanoparticles against amphotericin B-resistant Candida tropicalis

In recent years, cases of resistance to major antifungal drugs have been reported for Candida species. The growing resistance of fungi to conventional antifungal agents demands the development of new and effective antifungal strategies. Organosolv lignin-capped silver-based nanoparticles constitute a promising strategy, combining the antifungal activity of metallic silver with the biocompatibility and sustainability of organosolv lignin. In this context, we report a fast green photochemical method for synthesizing plasmonic silver/silver chloride nanoparticles capped with organosolv lignin (OL/Ag/AgCl-NPs) for antifungal applications. The OL/Ag/AgCl-NPs possess a well-defined spherical three-layered architecture, comprising a semiconductor AgCl core, an intermediate metallic silver surface, and a thin outer organosolv lignin layer. The cytotoxicity of the OL/Ag/AgCl-NPs in VERO cells was confirmed to be concentration-dependent. Crucially, cells exposed to toxic doses recovered metabolic activity comparable to controls, suggesting potentially reversible cytotoxic effects. The broad-spectrum antifungal agent Amphotericin B (AmB) effectively inhibited the growth of pathogenic Nakaseomyces glabratus (formerly Candida glabrata) and Pichia kudriavzevii (formerly Candida krusei), both displaying a minimum inhibitory concentration (MIC) of 0.19 µg/mL. In contrast, pathogenic Candida tropicalis exhibited resistance to AmB. Notably, OL/Ag/AgCl-NPs exhibited remarkable antifungal activity against N. glabratus, P. kudriavzevii, and AmB-resistant C. tropicalis, with MIC values of 1.09 µg/mL, 2.18 µg/mL, and 2.18 µg/mL, respectively. Moreover, the results revealed that the OL/Ag/AgCl-NPs exhibited a fungistatic effect against N. glabratus and P. kudriavzevii, while exhibited a fungicidal effect against the AmB-resistant C. tropicalis. These findings are particularly relevant given the challenge of treating resistant fungal infections and may contribute to the development of new therapeutic strategies. This study advances organosolv lignin-based nanomaterials, offering a promising platform for future biomedical applications.