The Research Of BODIPY-containing Nanoscale Metal-Organic Frameworks As Contrast Agents In Hepatocarcinoma Computed Tomography

Hepatocarcinoma is one of the common malignant tumor in our country,which seriously threatens people's health.At present,although the liver cancer patients' overall survival has been highly improved with the development of treatment,but there is still a high mortality of cancer,and the prevention form is still grim.High mortality of liver cancer is mainly attributed to the low early diagnosis rate and poor prognosis of advanced cancer treatment.The early diagnosis of tumor can greatly improve the prognosis of tumor patients after treatment.Computed Tomography(CT)has become an indispensable tool in clinical diagnosis for its unique characteristics of high spatial,density resolution,and deep tissue penetration.However,the attenuation values of different soft living tissues and organs usually display relatively high similarity,making it difficult to distinguish normal tissues and diseased tissues.Therefore,some of contrast agents contain heavy elements with high X-ray attenuation ability are necessary to obtain CT images with desired contrast enhancements.Conventional CT contrast agents in clinical practice are those small iodinated aromatic molecules.However,rapid pharmacokinetics,non-specific distribution and side effects have limited these materials in clinical diagnostic applications.The use of nanoscale metal-Organic frameworks as nanocarrier for iodine drugs could improve the targeted property of CT imaging and imaging effect,and also can reduce the drug dosage and decrease the side effects.Therefore,nanoscale metal-organic frameworks provide a new thought and opportunity for targeting diagnosis of malignant tumor.Objective:This study intends to synthesis BODIPY-containing Nanoscale Metal-OrganicFrameworks by solvent-assisted ligandexchange method(SALE).The biocompatibility of UiO-PDT nanoparticles is verified by MTT experiment on Hep G2 cells,blood compatibility test and toxicity test on kunming mice.SD rats bearing Walk 256 orthotopic hepatoma are intended to be prepared and the feasibility and excellent imaging effect of UiO-PDT used as CT contrast agent are intended to be vilified through the following aspects: contrast analysis with traditional small-molecule contrast agents meglumine diatrizoate,CT imaging in vitro and vivo.Method:(1)The carboxyl-functionalized diiodo-substituted BODIPYs(I2-BDP)is incorporated into the nanoscale UiO-MOFs(UiO-66)to exert the PDT into the final product of UiO-PDT by solvent-assisted ligand exchange method(SALE).The physicochemical properties are tested by 1H Proton nuclear magnetic resonance(1H NMR),transmission electron microscopy(TEM)? scanning electron microscope(SEM)? phase analysis of X ray diffraction(PXRD)and ultraviolet–visible spectroscopy(UV-vis).The CT imaging effect in vitro environment is tested by a Micro CT.(2)Anthropogenic cells Hep G2 are used as experiment cells.The cytotoxicity of UiO-PDT nanoparticales was detected by MTT method.The biological safety of UiO-PDT is verified through blood compatibility test and animal biocompatibility related experiments in vivo.(3)SD rats bearing Walk 256 orthotopic hepatoma are intended to be prepared.The overall evaluation of UiO-PDT nanocrystalline imaging effect and imaging change rule in vivo are carried out by the analysis of CT images and data post injection via tail vein.(4)By comparing the CT images of small molecule CT contrast agents meglumine diatrizoate in vivo orthotopic hepatoma SD rats,the advantages of UiO-PDT nanoparticles as contrast agents in hepatocarcinoma computed tomography are revealed.Result:(1)During the research,our team successfully synthesis nanoscale metal-organic frameworks(UiO-PDT).Octahedral structure of UiO-PDT is observed under TEMand SEM,and its particle size is about 70 nm.PXRD and UV-vis spectrum results suggest crystal stability of structure and the component of chemical composition.The Micro CT results of UiO-PDT in vitro shows that the CT values of nanocrystalline in vitro environment present a good linear relationship with concentration.(2)In the aspects of biocompatibility characterization,the superior biocompatibility characterization of UiO-PDT nanocrystalline is confirmed by MTT test on Hep G2 cells,blood compatibility tests in vitro(hemolysis experiment,plasma coagulation experiment)and kunming mice biocompatibility examinations in vivo(blood biochemical examination,histologic examination,weight change curve),and provided the theoretical basis for its clinical application.(3)In this study,SD rats bearing Walk 256 orthotopic hepatoma are successfully prepared.The CT imaging results of UiO-PDT in SD rats bearing Walk 256 orthotopic hepatoma shows UiO-PDT nanoparticles not only significantly prolong the circulation time in body,and also receive satisfactory results of the nanoparticles targeted gathering in hepatoma site,confirming that the idea for UiO-PDT as tumor CT contrast agenst was feasible,and had wide application prospects.(4)Compared with the small molecule CT contrast agents meglumine diatrizoate in vivo,UiO-PDT has a longer cycle time and a longer enhanced CT imaging time in the tumor sit.In the case of the same iodine content,the imaging contrast effect of UiO-PDT in hepatocarcinoma is better than the traditional small molecule contrast agents.Conclusion:(1)In this study,we successfully design and synthesize a new type of nanoscale CT contrast agent: BODIPY-containing nanoscale metal-organic frameworks,UiO-PDT.(2)UiO-PDT nanoparticles have a good biocompatibility and lays a solid foundation for further clinical application.(3)Compared with the traditional small molecule contrast agents,UiO-PDT has a longer cycle time in the body,CT enhanced imaging time and better effect of enhanced CT imaging in hepatocarcinoma,suggesting UiO-PDT as a feasible CT contrast agent in hepatocarcinoma and has a good application prospect.