Study On The Application Of Nanometallic Organic Frame Granule TCPC-UiO As CT Contrast Agent For Hepatocellular Carcinoma

Objective:To synthesize a novel nano-CT contrast agent TCPC-UiO and to study its biocompatibility and cytotoxicity.Mouse in situ liver cancer model was established by using murine CT26 colon cancer cell line.The feasibility of using nano-organometallic frame particle TCPC-UiO in liver cancer contrast medium was discussed by in vitro CT imaging of nano-materials and in vivo CT imaging of liver cancer.To provide the basis for further clinical application.Materials and methods:preparation and characterization of TCPC-UiO nanometallic organic framework particles: we successfully prepared TCPC-UiO nanocrystals.The physicochemical properties and in vitro CT imaging of TCPC-Ui O nanoparticles were analyzed by TEM,SEM,XRD,UV-vis spectra,PDI,Zeta potential and aqueous solution of nanocrystalline.Materials and methods:(1)Preparation and characterization of TCPC-UiO nanometallic organic framework particles: we successfully prepared TCPC-UiO nanocrystals.The physicochemical properties and in vitro CT imaging of TCPC-UiO nanoparticles were analyzed by TEM,SEM,XRD,UV-vis spectra,PDI,Zeta potential and aqueous solution of nanocrystalline.(2)Biocompatibility of organometallic framework nanoparticles(TCPC-UiO):the cytotoxicity of TCPC-UiO nanoparticles was detected by MTT assay in HepG2 cells of human liver cancer and Hela cells of cervical cancer.The blood compatibility of TCPC-UiO nanoparticles was tested by hemolysis test and plasmacoagulation test.Ten healthy male mice were randomly divided into experimental group and control group.Mice in experimental group were injected with TCPC-UiO nanoparticles through tail vein.Mice in the control group were injected with PBS solution.The body weight of the mice was recorded at 3 days,7 days,14 days and21 days after administration,and the blood routine examination and blood biochemical indexes were detected at the same time points in the experimental group and the control group.After 21 days,the mice were killed and dissected,and the important organs(heart,liver,spleen,lung and kidney)were taken for histopathological examination to further analyze the biocompatibility of nanoparticles in vivo.(3)In vivo CT imaging of organometallic framework nanoparticles(TCPC-UiO):a mouse model of liver cancer in situ was established.Nanoparticles were injected into the tail vein and scanned with Toshiba Activion 16 spiral CT.Coronal and 3D images were obtained by multiplanar reformation and 3D reconstruction to evaluate the imaging effect and density intensity of TCPC-UiO nanoparticles in hepatocellular carcinoma and normal liver parenchyma.Results:(1)The TCPC-Ui O nanocrystalline was successfully prepared.Its structure is similar to that of Hf-UiO-66,which fully extends the high stability of Hf-UiO-66,and has good dispersibility,no agglomeration,uniform particle size,and its diameter is about 80-120 nm,its morphology is uniform and stable.Positive octahedral structure,in vitro CT imaging found that TCPC-UiO solution CT value and concentration of a good linear relationship,which is the premise that TCPC-UiO can be used as a CT contrast agent.(2)The results of MTT assay showed that the hemolysis rate of TCPC-UiO was lower than that of TCPC-UiO even at the maximum concentration of TCPC-UiO(hemolytic negative),which proved that TCPC-UiO did not produce hemolyticreaction to red blood cells in blood.The results of plasma coagulation test showed that PT,APTT,FIB and TT of different concentrations of nano-samples were not significantly abnormal,which proved that TCPC-Ui O did not interfere with the endogenous and exogenous coagulation pathway of organisms,and the blood compatibility was good.The results of biocompatibility test in vivo showed that the blood routine and biochemical indexes of the experimental group and the control group were within the normal range,no obvious abnormal changes were observed,the weight of the mice grew slowly,consistent with the control group,and no obvious wasting was observed.The results of H & E staining of important tissues and organs in the experimental group and the control group were normal and no obvious tissue damage was found.The above experiments proved that the TCPC-UiO nanoparticles had very good biocompatibility.This provides a sufficient biological basis for its use as a CT contrast agent and provides the necessary theoretical basis for its clinical application in the future.(3)A mouse model of liver cancer in situ was successfully established.The results of CT imaging showed that TCPC-UiO nanoparticles could accumulate in the liver and liver cancer tissues,and the imaging effect was clear.We also found that the in vivo circulation time was very long and the body clearance rate was low.And has a very long development time,thus confirmed its feasibility as a CT contrast agent for liver cancer,and has a broad application prospects.Conclusion:(1)In this study,a novel nano-scale CT contrast agent,TCPC-UiO,was successfully prepared.(2)The biocompatibility of TCPC-UiO nanoparticles is good,which provides the possibility for its further wide application in clinic.(3)TCPC-UiO nanoparticles have a good effect on CT targeted imaging of liver cancer,with clear contrast,longer blood circulation time and imaging time thantraditional small molecular contrast agents,and no iodide.It provides the possibility for some patients with iodide hypersensitivity and renal insufficiency to use contrast agent and has a broad application prospect.