Novel Strategies Against Fungal Infections: Repurposing Existing Drugs and Advancing Nanotherapeutics

Fungal infections are rising globally, affecting nearly a quarter of the world's population. Driven by growing immunocompromised populations, the overuse of broad-spectrum antibiotics, and the emergence of multidrug-resistant fungi, conventional antifungal agents now face significant challenges in terms of efficacy, toxicity, and resistance. This review highlights emerging antifungal strategies, focusing on drug repurposing and nanomaterial-based approaches, in response to the growing challenge of fungal infections. Drug repurposing has revealed that numerous non-antifungal agents exhibited intrinsic antifungal activity or exerted strong synergistic effects combined with conventional antifungal drugs, thereby expanding the the therapeutic pipeline without requiring de novo drug discovery. Meanwhile, advanced polymeric and metallic nanomaterials offer key benefits, such as enhanced drug solubility, targeted delivery, improved biofilm penetration, multimodal fungicidal mechanisms, reduced host toxicity, and a lower propensity to induce resistance. Although most current studiesremain preclinical, the convergent advances in drug repurposing and nano-enabled antifungal technologies establish a promising route toward safer, more effective, and resistance-refractory therapies, underscoring the need for continued interdisciplinary innovation to accelerate clinical translation.