Application Of SCD1 Inhibitor-loaded Metal-polyphenol Nanomaterials To Induce Ferroptosis In Combination With Sonodynamic Therapy In The Diagnosis And Treatment Of Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma(ATC)has the characteristics of high malignant degree,rapid clinical progress and low five-year survival rate,which is a difficult problem in clinical treatment.Many researchers are committed to finding effective diagnosis and treatment strategies.The development and progress of nanomedicine bring new hope to ATC patients.Because surgery cannot be completely resected advanced ATC and is not sensitive to radiotherapy and chemotherapy,a single treatment method cannot meet clinical needs.Therefore,the collaborative treatment of multiple methods and the integration of diagnosis and treatment have become the inevitable trend of ATC research and development.In order to meet the current status of ATC,improve the problem of poor specificity of treatment program and difficult evaluation of therapeutic effect,this study developed a kind of SCD1-carrying metal-polyphenol nanoparticles that can target ATC tumors.The nanoparticle can induce ferroptosis of tumor cells and get Sonodynamic therapy(SDT)function under the action of Low intensity focused ultrasound(LIFU).It kills ATC tumor cells under the synergistic action of ferroptosis and SDT.In addition,the nanoparticle also has dual-modal imaging function,which can facilitate the comprehensive evaluation of tumor progression and therapeutic effect.Objective:To prepare IR825-modified iron-Tannic acid(TA)nanoparticles loaded with SCD1 inhibitors,detect their basic physicochemical properties,and evaluate their therapeutic effect and imaging ability through in vitro and in vivo experiments.Methods:six hydrated ferric chloride(FeCl3·6H2O),TA and mixed MF-438,adopt the method of magnetic stirring synthetic FTMP nanoparticles,and the nanoparticle surface was modified by IR825.Its basic physical and chemical properties were detected,including morphology,particle size,potential,stability,encapsulation rate,drug loading rate,glutathione(GSH)release and multimodal imaging capability.The ferroptosis and the SDT ability test,including reactive oxygen species(Reactive oxygen species,ROS)such as ·OH and 1O2.In vitro experiments,human ATC tumor BHT-101 cell line was used as the experimental group,and the safety,phagocytosis,toxicity,SDT and ferroptosis induction ability of nanoparticles were detected by CCK-8 method,fluorescence confocal microscopy and flow cytometry.In vivo experiments,BALB/c nude mice were used to test the biological safety,and the tumor therapeutic efficacy of ATC tumor bearing mice were evaluated.The dual-mode imaging ability of nanoparticles was evaluated by fluorescence and MRI imaging.Results:FTMP-IR nanoparticles containing SCD1 were modified by IR825 with ATC targeting capability were prepared successfully.The nanoparticle has uniform particle size,good dispersion and stability,and satisfactory encapsulation rate and load rate.It can be disassembled in GSH solution and release iron ion and MF-438,which has excellent ROS production capacity.In vitro and in vivo experiments confirmed that the nanoparticle could induce ferroptosis of ATC tumor.As a sound sensitizer,combined with LIFU showed excellent therapeutic effect and could completely eradicate tumor tissue.In terms of dual-mode imaging,FTMP-IR’s tumor targeting ability also determines its specificity in tumor site concentration and development,as FTMP-IR can be imaged under fluorescence and MRI.Conclusion:FTMP-IR nanoparticles prepared in this study can induce ferroptosis and the sonodynamic effect,which has a good killing effect on ATC tumors.At the same time,the nanoparticle has the function of dual-modal imaging,which is helpful to the evaluation of tumor progression and therapeutic effect.