Mycogenic Nanomaterials: What Fungal Nanoparticles Promise and What Still Holds Them Back.

Mycogenic nanomaterials, nanoparticles (NPs) biosynthesized through fungal enzymatic and metabolic activity, have emerged as a compelling alternative to chemically synthesized nanomaterials, offering fundamental biocompatibility, green production conditions, and biologically functional surface coatings. Fungi, acting as natural "nanofactories," harness reductases, oxidoreductases, secreted proteins, and secondary metabolites to reduce metal ions into stable NPs under ambient conditions, simultaneously capping the particles with biomolecules that enhance colloidal stability, biocompatibility, and secondary biological activity. Unlike previous reviews that have addressed either biosynthesis mechanisms or applications in isolation, this review uniquely adopts a structured "Promise vs. Barrier" framework across six interconnected thematic pillars, offering the first comprehensive critical synthesis that simultaneously maps mechanistic frontiers, biodiversity gaps, and translational barriers within mycogenic nanotechnology. The present review critically examines both the extraordinary promise and the persistent barriers facing mycogenic nanotechnology across biosynthetic mechanisms, fungal biodiversity, nanomaterial portfolio expansion, biomedical applications, environmental and agricultural utility, and industrial scalability. We highlight how emerging multiomics approaches, integrating transcriptomics, proteomics, and metabolomics, are beginning to decode the molecular blueprints of fungal NP synthesis, while acknowledging that mechanistic knowledge gaps, limited genetic toolkits for non-model fungi, and the absence of standardized protocols continue to impede progress. The fungal kingdom represents a vast, underexplored reservoir of nanofactory potential, with fewer than 1% of known species evaluated to date; strategic bioprospecting using genome mining and machine learning is beginning to unlock this diversity. Mycogenic NPs demonstrate broad-spectrum antimicrobial activity against multidrug-resistant pathogens, selective anticancer activity, biosensing capacity, and applications in wound healing, sustainable agriculture, environmental remediation, and smart food packaging. However, critical deficits persist in clinical validation, long-term toxicity data, manufacturing reproducibility, and regulatory clarity. The review concludes with a tiered roadmap, spanning immediate mechanistic priorities through to long-term synthetic biology and AI-integrated commercialization, and calls for coordinated international action on standardization, reference material development, and harmonized regulatory frameworks to bridge the gap between laboratory promise and real-world application.