Effective Combination of Isoniazid and Core-Shell Magnetic Nanoradiotherapy Against Gastrointestinal Tumor Cell Types

Abstract

Introduction: Radiotherapy is a conventional treatment for gastrointestinal tumors. However, its therapeutic effect might not be satisfactory because of factors such as radio-resistance of tumor cells and dose reduction applied to avoid damage to normal tissues. We developed a novel combination therapy involving the use of isoniazid (INH) and core-shell magnetic nanospheres (NPs) to enhance the efficacy of radiotherapy. Methods: Magnetic core-shell NPs were synthesized. The shell manganese dioxide (MnO2 ) reacted with intracellular glutathione to produce Mn2+, which decomposed hydrogen peroxide (H2 O2 ) to hydroxyl radicals (·OH) in the presence of INH to produce sufficient amount of reactive oxygen species. In addition to this chemodynamic therapy, MnO2 catalyzed H2O2 to O2, which alleviated hypoxia in tumors and thus enhanced the effect of radiotherapy. In addition, iron oxide (Fe3O4) and reduced Mn2+ were potential candidates for T1 –T2 dual-mode magnetic resonance imaging (MRI) with remarkable magnetic targeting ability. Results: NPs exhibited efficient tumor targeting performance under the magnetic field and improved T1 /T2 dual-mode MRI, which elevated oxygen levels without toxicity to the mice to achieve remarkable therapeutic outcomes, reaching a tumor inhibition rate of 93.2%. Moreover, chemodynamic therapy mediated by INH and NPs enhanced the therapeutic effect of radiotherapy both in vivo and in vitro. Conclusion: The results demonstrated that the combination of INH and NPs could be a novel strategy for radiosensitization with clinical potential.