The Phase-transition Nanoparticles For Multimodal Imaging And Combined Treatment For Thyroid Papillary Carcinoma

Background:Papillary thyroid carcinoma（PTC）is one of the most common malignant tumors in China.At present,there is no single,non-invasive examination method that can accurately characterize PTC in clinical practice,and there are still many disputes and disagreements on whether there is overtreatment and how to preserve thyroid function.With the development of nanotechnology,in order to achieve accurate imaging and treatment of PTC,in this study,we used polymer PLGA-COOH as the shell material,and ferric oxide（Fe₃O₄）,porphin e6（Ce6）,doxorucin（DOX）and perfluoropentane（PFP）as reaction elements.Multifunctional nanoparticles with magnetotaxis enrichment ability were successfully prepared.The nanoparticle not only realizes multi-modal imaging of ultrasound,magnetic resonance and fluorescence to improve the diagnostic accuracy of tumors,but also realizes the combination treatment of photothermal,photodynamic and chemotherapy for tumors,providing more research ideas for the diagnosis and treatment of PTC.Objective:The polymer PLGA-COOH was used as the shell material.Fe₃O₄,Ce6 and DOX were embedded in the shell,and the shell core was coated with PFP.The phase variant DOX-PFP@Fe₃O₄-Ce6-PLGA NPs（FCDP NPs）was prepared.To test its characterization and basic properties,evaluate the imaging ability and anti-tumor ability of nanoparticles in vitro,and study the multi-modal imaging ability of nanoparticles in vivo and the effect of multiple methods of combined therapy.Methods:Under the condition of ice bath,the polymer PLGA-COOH was used as the shell material,Fe₃O₄,Ce6 and DOX were embedded in the shell by double emulsification method,and the core of the nanoparticles was coated with PFP,to prepare the FCDP phase variant nanoparticles with magnetotactic enrichment.In the material science experiment,the characterization of FCDP nanoparticles was tested,including morphology,transmission particle size,hydration particle size,dispersion,potential and stability.Then the basic properties of the test,including: encapsulation rate,drug load determination and drug release;Detection of photothermal performance,photodynamic singlet oxygen performance detection;Magnetotaxis enrichment performance detection;The process of photoinduced phase transition under light microscope.To verify the evaluation and validation of ultrasonic imaging,magnetic resonance imaging and fluorescence imaging capabilities of nanoparticles in B-Mode and contrast-enhanced ultrasound（CEUS）mode.In vitro experiments,CCK-8 method was used to detect the effect of each component of nanoparticles on cell activity and the overall cytotoxicity of nanoparticles.Detection of nanoparticle cytophagocytosis to determine the best treatment time window;The effect of photothermal therapy and the production of photodynamic singlet oxygen were detected.Apoptosis was detected to evaluate the effect of combination therapy at the cellular level.In vivo experiments,the in vivo biosafety of nanoparticles was detected,the body weight,tumor length,diameter and volume of tumor-bearing nude mice under different group treatment were dynamically monitored,and the tumor growth curve was plotted.After the treatment,the tumor body was taken for pathological analysis to evaluate the effect of nanoparticle combined therapy in vivo.Results:FCDP nanoparticles were successfully prepared.The nanoparticles were spot-like under light microscope,spherical in shape under transmission electron microscope and scanning electron microscope,spherical in shape,uniform in size,uniform in distribution,negative potential,good stability and magnetotaxis enrichment ability.It was confirmed that Fe₃O₄,DOX and Ce6 had been successfully loaded,and had good photothermal efficiency and singlet oxygen production ability.FCDP nanoparticles can realize ultrasonic imaging,magnetic resonance imaging and fluorescence imaging both in vivo and in vitro,and the effect is excellent.In vivo and in vitro experiments,FCDP nanoparticles have good biosafety.FCDP can significantly inhibit tumor after applying 660 nm and 808 nm near-infrared light irradiation,and the therapeutic effect is the best,and the difference is statistically significant.Conclusion:In this study,we successfully prepared the homogeneous size,good dispersion,stable property,magnetotaxis enrichment and biosafety phase variant nanoparticle FCDP,which has the capabilities of ultrasonic imaging,magnetic resonance imaging and fluorescence imaging,as well as photothermal,photodynamic and chemotherapy combined therapy.It provides more new ideas and suggestions for clinical diagnosis and treatment of PTC.