Dual antifungal activity against Candida albicans of copper metallic nanostructures and hierarchical copper oxide marigold-like nanostructures grown in situ in the culture medium

Aims: This study aimed to determine in vitro activity of copper nanoparticles and copper nanowires against C. albicans strains and to assess their effects on morphology and sub-micron structure.

Methods and results: The microdilution method determined the minimal inhibitory concentration (MIC) of copper nanoparticles (CuNPs) and copper nanowires (CuNWs) against three strains of C. albicans: ATCC 10231 and two clinical strains (C and E). Effects on the morphology and ultrastructure of C. albicans strains were examined by scanning electron microscopy and transmission electron microscopy. MIC for CuNPs was 129.7 µg/mL for strain ATCC 10231, 1037.5 µg/mL for strain C and 518.8 µg/mL for strain E. MIC for CuNWs was similar for all strains tested (260.3 µg/mL). SEM and TEM studies showed alterations in morphology, cell wall, and the complete collapse of the yeast after incubation with CuNPs. In contrast, most of the yeast cells maintained their structure with an intact cell wall, and only decreased the number and size of fimbriae when C. albicans was exposed to CuNWs. CuNPs and CuNWs formed hierarchical copper oxide nanostructures growing in situ in the culture medium. Results suggest a dual mechanism for antifungal activity: a) free Cu²⁺ ions act as a biocide, b) sharp edges of marigold-like petal nanostructures could injure the cellular wall and membrane and cause the death of the yeast.

Conclusions: CuNPs and CuNWs inhibited the growth of the three strains of C. albicans tested. Moreover, CuNPs disrupted cell wall with leakage of the cytoplasmic content. Each concentration of the series used for the determination of the activity of copper nanoparticles and nanowires against C. albicans formed copper oxide marigold-like nanostructures.

Significance and impact: This study suggests that CuNPs and CuNWs are good candidates for formulating new therapeutic agents for candidiasis.

Keywords: Candida albicans; antifungal; copper; hierarchical; nanostructure.