Evaluation of radiation sensitivity of iron-based metal organic frameworks loaded with paclitaxel in breast cancer radiation therapy

Abstract

Cancer stands as a significant contributor to mortality worldwide. Among the primary reasons for the lack of treatment success and tumor recurrence is the development of resistance to therapeutic methods. Utilizing innovative and targeted approaches through the design of purposeful nanostructures with multifunctional applications that enhance drug effects and improve the impact of radiation in chemoradiotherapy can play a valuable role. This study aims to synthesize and investigate the synergistic effects and radiation sensitivity resulting from organic-inorganic frameworks based on iron ions (Fe-MOFs). These frameworks are capable of encapsulating paclitaxel (PTX) drug, coated with BSA, and applied in radiation therapy for MCF-7 breast cancer cell line. Method and materials: This study was conducted in the laboratory environment of the Nutrition Research Center, utilizing the MCF-7 breast cancer cell line. Cancer cells were cultured in RPMI medium supplemented with 10% fetal bovine serum at 37°C and 5% CO2. Iron-based MOF nanoparticles carrying the chemotherapeutic drug paclitaxel (PTX) with BSA coating were synthesized as radiation sensitizers and ROS-inducing agents. Subsequently, the physical and chemical properties of the nanostructures were evaluated using techniques such as DLS, TEM, XRD, and FT-IR . Additionally, hemocompatibility was assessed using hemolysis testing. The cellular study groups comprised a control group, a group undergoing PTX treatment, groups treated with nano Fe-MOFs, and Fe-MOF@PTX, which were examined in the presence and absence of radiation. Prepared samples were transferred to the Civil Hospital for radiation exposure at doses of 2,4, and 8 Gy, using energies of 6 and 15 megavolts. Subsequently, assays including Uptake, MTT, Apoptosis, DAPI, and ROS were employed to determine cell survival rates, anticancer effects, and increased radiation sensitivity. Results: Physicochemical property determination experiments indicated that the hydrodynamic diameter of the synthesized Fe-MOF@PTX-BSA nanostructure was 78.80 ± 8.362 nm, with a zeta potential of 11.6 ± 3.13 mV. TEM imaging of the final nanostructure revealed uniform particle size of approximately 72 nm. Successful drug loading was evaluated and confirmed through FT-IR, XRD analyses, and drug release assessments. The Fe-MOF-BSA nanostructure exhibited suitable hemolytic properties at various concentrations. MTT assays displayed significant cellular toxicity in cells treated with the MOF nanosystem, final nanostructure, and PTX drug compared to untreated cells. The anticancer effects and increased radiation sensitivity of the nanosystem and final nanostructure were validated under both irradiated and non-irradiated conditions using MTT, Apoptosis, and DAPI assays. Overall, cell death and apoptosis resulting from a substantial induction of ROS were observed in cancer cells treated with the nanosystem and final nanostructure in conjunction with X-ray radiation.