Fe²⁺-activated reactive oxygen species amplification via metal-organic frameworks loaded with paclitaxel for enhanced radiosensitivity in breast cancer radiotherapy.

Cancer stands as a significant contributor to global mortality. Innovative and targeted strategies, particularly the design of purposeful nanostructures with multifunctional applications, have gained interest in chemo-radiotherapy. This approach aims to enhance the radio-sensitization of tumor tissues while concurrently reducing unnecessary damage to surrounding healthy organs. This study aimed to synthesize ferrous-based metal-organic frameworks (Fe-MOF), a class of hybrid nanomaterials consisting of Fe²⁺ ions and organic ligands, loaded with paclitaxel (PTX) and coated with Bovine Serum Albumin (BSA), to investigate their effects at different doses of X-ray radiation on Human breast epithelial adenocarcinoma (MCF-7) cells. Fe-MOFs were evaluated as a potential drug-releasing nanoparticle, aiming to enhance PTX solubility and promote radiation sensitivity in the MCF-7 breast cancer cell line during radiotherapy. The successful synthesis of Fe-MOF@PTX-BSA and drug loading were confirmed by DLS, TEM, FT-IR, XRD, and BET analyses. Anticancer effects and enhanced radio-sensitivity were validated using MTT, apoptosis, and DAPI assays under irradiated (6MV) and non-irradiated conditions. Fe-MOF@BSA nanoparticles exhibited suitable hemolytic properties at various concentrations. After successfully demonstrating the efficient cellular uptake of nMOFs, in vitro experiments showed that Fe-MOF@PTX-BSA, along with X-ray radiation, activated substantial in situ generation of ROS, leading to increased radio-sensitivity and apoptosis in MCF-7 cells. Therefore, Fe-MOF@PTX-BSA shows potential as both a drug carrier and radiosensitizer for future in vivo studies.