Synthesis and characterization of chitosan-coated silver metal–organic frameworks as pH-responsive carriers for doxorubicin release and enhanced anticancer activity

The present work focuses on a rapid and facile hydrothermal synthesis of a silver metal–organic framework (Ag-MOF) using 2-methylimidazole linker and silver nitrate. The anticancer drug doxorubicin (DOX) was successfully loaded on Ag-MOF and further coated with chitosan (CS) to enhance stability and pH-responsive drug release. Physicochemical characterization employing X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and zeta potential confirmed the successful synthesis, drug loading, CS coating and stability of the formulation. Scanning electron microscopy (SEM) established that MOF nanoparticles were densely packed quasi-spherical nanoparticles (200-400nm). In vitro drug-release analysis presented a pronounced pH-dependent behavior, with cumulative DOX release reaching approximately 87% at pH 5.5 compared to ∼30% at pH 7.4 over 48 h, representing effective acidic tumor-responsive release. The DOX@Ag-MOF-CS formulation also exhibited improved stability under simulated gastric and alkaline conditions. Furthermore, MTT assay outcomes showed concentration-dependent selective cytotoxicity against HepG2 cells, with DOX@Ag-MOF-CS inducing up to ∼64% cell death at 100 µg/mL, surpassing uncoated DOX@Ag-MOF while maintaining controlled toxicity. Overall, DOX@Ag-MOF-CS represents a promising pH-responsive nanocarrier for targeted anticancer drug delivery.