Preparation And Properties Of Ferrocene-substituted Polyacid Magnetic Contrast Agents

Cancer is one of the most common high-incidence diseases of human mortality.It is a serious threat to people's health.The rapid development of high-efficient and non-radioactive magnetic resonance imaging technology provides great convenience for the diagnosis and even early diagnosis of diseases such as cancer.The use of nuclear magnetic resonance contrast agents to improve imaging contrast and sharpness can greatly enhance the detection rate of lesions or tissue imaging of nuclear magnetic resonance imaging technology.MRI contrast agents show great clinical application value.At present,various contrast agents synthesized by coordination of small molecular or macromolecular materials with metal ions have been developed for use in nuclear magnetic resonance imaging.However,the synthesis of macromolecular contrast agents with high relaxation efficiency,low toxicity,good water solubility,and long body residence time is still a huge problem.In this thesis,two novel polyoxometalates-based nuclear magnetic contrast agents,which include ferrocene-substituted Keggin-type POMs PW₁₁-APTMS-Fc A and iron-coordinated Dawson-type POMs Fe₄^?(P₂W₁₅)₂ were designed and synthesized.These two materials were characterized by Fourier transform infrared spectroscopy,nuclear magnetic resonance spectroscopy,Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry and electrochemical tests.The results confirmed the successful preparation of novel nuclear magnetic contrast agents.In vitro cytotoxicity of PW₁₁-APTMS-Fc A and Fe₄^?(P₂W₁₅)₂ were measured by MTT assay.MTT assay results showed that normal cells HUVEC could maintain cell viability of 82% to 93% at a working concentration of 10?M.Furthermore Fe₄^?(P₂W₁₅)₂ exhibited lower cytotoxicity?93%?.In addition,hepatocarcinoma cells Hpe G-2 showed very low activity at high concentration of MRI contrast agents?8 14%?.The ability of both MRI contrast agents to relax in vivo and in vitro was tested using Micro MR.In vitro results showed that PW₁₁-APTMS-Fc Aand Fe₄^?(P₂W₁₅)₂ had a T2 relaxation efficiency of 5.71 m M-1s-1and 10.23 m M-1s-1,respectively,which are1.03 and 1.93 times of commercial contrast agent,Gd-DTPA,respectively.After tail vein injecting,the T2 nuclear magnetic signal in mice showed strong-weak-strong trend.Among them,PW₁₁-APTMS-Fc A had the most significant changes in signal intensity in the liver and tumor tissues,and had a longer duration in vivo.Fe₄^?(P₂W₁₅)₂ had the most significant changes in signal intensity in the liver,brain,muscle,and tumor tissues,and its duration was slightly shorter,but the imaging enhancement ability was stronger.Pathological analysis,routine blood test and body weight monitoring all showed that thenuclear magnetic contrast agents PW₁₁-APTMS-Fc A and Fe₄^?(P₂W₁₅)₂ had no obvious toxicity to the major organs of mice and had good biosafety.At the same time,ICP-OES analysis showed that both contrast agents could be gradually metabolized in vivo,and the main metabolic organs are liver,spleen,and kidney.In summary,the new nuclear magnetic contrast agents prepared in this thesis had high contrast enhancement capability and low toxicity.They could passively target the liver and tumor tissues.Moreover,they had appropriate retention time in the bodyand could be easily eliminated from the body.These two MRI contrast agentswere expected to be used for clinical magnetic resonance imaging diagnosis.