Magnetic field-guided hollow mesoporous magnetite nanoparticles for enhanced sonodynamic therapy

Pancreatic cancer is highly vulnerable to ferroptosis. Consequently, treatments that target pancreatic cancer through ferroptosis induction demonstrate immense potential for enhancing therapeutic outcomes in this condition. In the present study, we synthesized hollow mesoporous iron oxide nanoparticles (MHFe) using a hydrothermal method. These nanoparticles retained the superparamagnetic properties of iron oxide and its Fenton reaction-catalyzing ability. Meanwhile, they also showed superior drug-loading capacity compared to traditional ferric oxide nanoparticles due to their hollow and mesoporous structure. Under the guidance of a magnetic field, these nanoparticles could accumulate in tumor cells. Following the incorporation of Ce6, a sonosensitizer, the Ce6@MHFe system could generate singlet oxygen under ultrasound treatment to promote tumor cell apoptosis while simultaneously producing hydroxyl radicals through the enhanced Fenton effect of MHFe. This promoted ferroptosis in pancreatic cancer cells, achieving combined therapeutic effects. In vivo experiments confirmed the good biocompatibility of Ce6@MHFe and demonstrated that the nanoparticles could effectively kill tumor cells under magnetic targeting and ultrasound irradiation, thereby inhibiting tumor growth. The findings suggested that these hollow mesoporous iron oxide nanoparticles (Ce6@MHFe) with a high drug-loading capacity, tumor retention ability, and potential for combination therapy have potential for the treatment of various malignancies, including pancreatic cancer.