Dual‐Functioning Metal‐Organic Frameworks: Methotrexate‐Loaded Gadolinium MOFs as Drug Carriers and Radiosensitizers

Cancer remains a critical global health challenge, necessitating advanced drug delivery systems through innovations in materials science and nanotechnology. This study evaluates gadolinium metal-organic frameworks (Gd-MOFs) as potential drug delivery systems for anticancer therapy, particularly when combined with radiotherapy. Gd-MOFs were synthesized using terephthalic acid and gadolinium (III) chloride hexahydrate and then loaded with methotrexate (MTX). Characterization via fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), magnetic resonance imaging (MRI), and X-ray diffraction (XRD) confirmed their correct structure and stability. Effective MTX loading and controlled release were demonstrated. Anticancer effects were assessed on human healthy bronchial epithelial cells (BEAS-2B) and human lung cancer cells (A549) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay under in vitro radiation therapy. MTX/Gd-MOF combined with radiotherapy showed a greater reduction in cancer cell viability (41.89% ± 2.75 for A549) compared to healthy cells (56.80% ± 1.97 for BEAS-2B), indicating selective cytotoxicity. These findings highlight the potential of Gd-MOFs not only as drug delivery vehicles but also as radiosensitizers, enhancing radiotherapy efficacy and offering promising evidence for their use in combinatory cancer therapies to improve treatment outcomes.