Ce-Based MOFs Coated with Carbon Nanotubes for pH-Controlled Release of Antifungal Agents

This study reports a novel redox-responsive and pH-sensitive nanohybrid system, Ce-MOF@CNT, designed for the controlled delivery of sodium lignosulfonate (SLS) with enhanced antifungal efficacy against Aspergillus fumigatus. The hybrid integrates cerium-based metal–organic frameworks (Ce-MOFs) with functionalized carbon nanotubes (FCNTs), enabling high drug loading (88%) and sustained release (∼87.5% at pH 5.0), governed by non-Fickian diffusion (Korsmeyer–Peppas, R2 = 0.9819). Comprehensive physicochemical characterization via FE-SEM, HR-TEM, FTIR, XPS, XRD, and BET (surface area: 906.15 m2/g) confirmed the successful synthesis and structural integrity. Zeta potential (−36 mV) and TGA (residual mass ∼44% at 600 °C) verified colloidal and thermal stability. The nanohybrid exhibited superior antifungal activity with a MIC50 of 3.46 mg/mL, outperforming Ce-MOF-CNTs (MIC50 = 4.24 mg/mL) and comparable to caspofungin (MIC50 = 4.56 mg/mL). The maximum inhibition zone reached 3.4 ± 0.1 cm at 100 mg/mL. SEM analysis revealed fungal membrane collapse, and peroxidase-mimetic assays confirmed ROS generation via Ce3+/Ce4+ cycling. Transcriptomic profiling showed extensive dysregulation of redox and membrane-associated genes, including upregulation of enrichment in amino acid metabolic processes (↑3.67-fold) and suppression of ergosterol synthesis genes. The novelty lies in the integration of an anionic novel antifungal agent (SLS) into a redox-active, mesoporous Ce-MOF-CNT scaffold, enabling synergistic antifungal action through mechanical disruption, oxidative stress, and pH-triggered release. This work offers a promising multifunctional nanoplatform for next-generation antifungal therapy and establishes a precedent for lignin-derived drug delivery systems.