[Salphen-Based Fe-NO@C Nanomaterial Applied in Synergistic Sonodynamic and Chemodynamic Therapy of Tumors].

OBJECTIVE

To synthesize a Salphen-based Fe-NO@C material with high peroxidase (POD)-mimicking activity and sonosensitivity for the synergistic sonodynamic (SDT) and chemodynamic (CDT) therapy of tumors.

METHODS

Fe-NO was synthesized via the hydrothermal method, and Fe-NO@C was prepared by incorporating a ketjen black substrate. The morphology, structure, composition, enzyme mimic activity for reactive oxygen species (ROS) production, and sonosensitivity of the material were characterized. The ability and mechanism of Fe-NO@C to perform synergistic SDT and CDT killing of 4T1 mouse breast cancer cells were explored through experiments. The tumor-killing ability of Fe-NO@C combined with ultrasound irradiation was investigated using a subcutaneous 4T1 tumor-bearing mouse model.

RESULTS

FFe-NO and Fe-NO@C were both irregularly shaped nanospheres with average particle sizes of 25.9 nm and 36.2 nm, respectively. XRD, FTIR, and XPS analyses confirmed that both Fe-NO and Fe-NO@C possessed a Salphen covalent organic framework structure with M-NO coordination, and the ketjen black loading had no significant impact on this structure. Compared to Fe-NO, Fe-NO@C exhibited high POD-mimicking activity (with reduced from 19.32 to 5.82 mmol/L and increased from 2.51×10 to 8.92×10 mol/[L·s]) and sonosensitivity. Fe-NO@C in combination with ultrasound irradiation could produce a large amount of ROS within cells and a subsequent significant decrease in mitochondrial membrane potential, thereby inducing TEM-observable mitochondrial damage and causing cell apoptosis and death. In addition, experiments showed that Fe-NO@C in combination with ultrasound irradiation could effectively inhibit tumor growth in a 4T1 subcutaneous tumor-bearing mouse model without significant toxicity.

CONCLUSION

In this study, we prepared a Salphen-based Fe-NO@C material with good biocompatibility, which can be used in combination with ultrasound irradiation to achieve SDT and CDT synergistic killing of tumor cells and inhibit tumor growth. This Salphen-based Fe-NO@C nanomaterial shows promising potential for multimodal tumor therapy.