Salphen-Based Fe-N2O2@C Nanomaterial Applied in Synergistic Sonodynamic and Chemodynamic Therapy of Tumors
Objective To synthesize a Salphen-based Fe-N2O2@C material with high peroxidase(POD)-mimicking activity and sonosensitivity for the synergistic sonodynamic(SDT)and chemodynamic(CDT)therapy of tumors.Methods Fe-N2O2 was synthesized via the hydrothermal method,and Fe-N2O2@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-N2O2@C to perform synergistic SDT and CDT killing of 4T1 mouse breast cancer cells were explored through in vitro experiments.The in vivo tumor-killing ability of Fe-N2O2@C combined with ultrasound irradiation was investigated using a subcutaneous 4T1 tumor-bearing mouse model.Results FFe-N2O2 and Fe-N2O2@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-N2O2 and Fe-N2O2@C possessed a Salphen covalent organic framework structure with M-N2O2 coordination,and the ketjen black loading had no significant impact on this structure.Compared to Fe-N2O2,Fe-N2O2@C exhibited high POD-mimicking activity(with Km reduced from 19.32 to 5.82 mmol/L and vmax increased from 2.51×10-8 to 8.92×10-8 mol/[L·s])and sonosensitivity.Fe-N2O2@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,in vivo experiments showed that Fe-N2O2@C in combination with ultrasound irradiation could effectively inhibit tumor growth in a 4T1 subcutaneous tumor-bearing mouse model without significant in vivo toxicity.Conclusion In this study,we prepared a Salphen-based Fe-N2O2@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-N2O2@C nanomaterial shows promising potential for multimodal tumor therapy.
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