Emerging antifungal strategies against Candida albicans using metal-organic frameworks and novel therapeutics:...

Candida albicans is an opportunistic fungal pathogen responsible for infections ranging from superficial mucosal disease to life-threatening systemic candidiasis, particularly in immunocompromised hosts. Its pathogenicity is enhanced by morphological plasticity, biofilm formation, and immune evasion, contributing to antifungal resistance. Limitations of existing antifungals have driven interest in emerging therapeutics. This review highlights strategies including metal-organic frameworks (MOFs), host-directed therapies (HDTs), CRISPR-Cas9 gene editing, and phytochemicals. MOFs offer high drug-loading capacity, controlled release, and enhanced penetration into biofilms, showing promise against drug-resistant strains. Selected phytochemicals demonstrate inhibitory effects on virulence traits such as hyphal formation and enzyme secretion. CRISPR-Cas9 enables functional genomic studies to identify and disrupt key pathogenicity genes, while HDTs aim to boost host immune responses. Additionally, the potential role of gut microbiota modulation in controlling C. albicans colonization is discussed. By integrating mechanistic insights with translational perspectives, this review provides a concise overview of emerging antifungal strategies, opportunities, and challenges with the potential to overcome current therapeutic limitations.