Zinc oxide nanoparticles against Candida: mechanistic pathways, synergistic potentials, and biocompatibility challenges in the era of antimicrobial resistance.

The emergence of antifungal resistance among diverse Candida species highlights the need for a more efficient and effective approach to address this issue. Nanotechnology has emerged as a transformative approach with great promise to counter antifungal resistance, a global concern that has surged over the past two decades. Antifungal activity of zinc oxide nanoparticles (ZnO NPs), their green synthesis approaches, and mechanisms of action are promising characteristics that warrant systematic investigation. This review discusses the current literature available on ZnO NPs focusing on the approaches used in the synthesis of these nanoparticles, characterization, antifungal efficacy of these nanoparticles against Candida species, mechanisms of action, and effects on biofilm formation, potential synergistic effects with antifungal compounds, as well as their biocompatibility. From 324 PubMed and 688 Scopus records, 44 and 66 articles, respectively, were screened; after exclusions, 33 original studies (20 from Scopus and 13 from PubMed) were included in this review. Based on reviewed studies, ZnO NPs demonstrate antifungal activity against several Candida species, such as Candida albicans, C. glabrata, C. auris, C. tropicalis, C. parapsilosis, C. krusei, and C. famata, and the possible mechanisms of action of ZnO NPs are reactive oxygen species production, release of Zn²+ ions, cell membrane disruption, oxidative stress induction, inhibition of biofilm formation, and suppression of virulence genes. The green synthesis of ZnO NPs exhibited all but one of the traits required for biocompatibility. Their combination with standard antifungals enhanced antifungal activity. ZnO NPs therefore represent a promising antifungal strategy for the treatment of candidiasis. To ensure safety and therapeutic applicability, however, additional validation through standardized research, pharmacokinetic and toxicological evaluations, and well-designed clinical trials is necessary.