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 (H₂O₂) 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.
Keywords: chemodynamic therapy, Fenton-like, isoniazid, radiotherapy, magnetic resonance imaging