Insights on nanomaterials-fungi interactions: probing engineering principles for developing antifungal nanomedicines.

Fungal infections are a growing healthcare concern worldwide. Aspergillus, Candida and Cryptococcus are considered the most important genera of human pathogenic fungi and treatment of their infections is often challenging. The limited efficacy of available antifungal drugs is largely associated with toxicity and the rising rates of resistance. Thus, alternative therapeutic modalities such as the utilization of nanomedicines have emerged and even introduced in clinical practice. These antifungal nanosystems have been explored as drug delivery systems and/or as intrinsic antifungal agents. Although the establishment of direct interactions between nanomaterials and fungi is recognized as being important for activity and, ultimately, clinical success, such matter remains poorly understood. Mechanisms of action leading to fungi inhibition or death upon exposure to antifungal nanomaterials are quite diverse and include cell wall and membrane bonding, structural damage, metabolic changes and genotoxicity. The present review discusses current knowledge on the main mechanisms involved in nanomaterials-fungi interactions, with an emphasis on cell damage processes, while providing relevant hints for the prospective design of innovative antifungal nanomedicines.