Preparation Of Multifunctional Nanoprobe And Its Application Performance In Diagnosis And Treatment Of Atherosclerosis

Most acute cardiovascular diseases are caused by the rupture or erosion of atherosclerotic（AS）plaques,which form arterial thrombi,resulting in arterial blockage or rupture.According to the severity of the disease,the treatment of atherosclerosis can be divided into surgical treatment and drug treatment.Surgical treatment is usually used in the middle and late stages of disease development,and there is a large risk.Therefore,more medication is used in the middle and early stages of disease development.Since nanoparticles have provided safer and more effective chemotherapy drugs for the treatment of cancer,nanoparticles have been extensively researched to treat various diseases,which has also shown great potential and hope in the fight against cardiovascular diseases.Nano delivery systems deliver imaging agents or drugs to a target site for diagnostic imaging or treatment of various diseases,providing new insights into the detection and treatment of atherosclerosis.Based on the pathological characteristics of atherosclerosis,this thesis designed a probe that can be used for MRI dual-modality imaging.The nano-delivery system is designed to provide a new approach for exploring the diagnosis and treatment of cardiovascular diseases such as atherosclerosis.Firstly,a dual-mode probe was prepared by combining carbon quantum dots synthesized by superparamagnetic iron oxide and citric acid.And then the infrared,magnetic and fluorescent detection of the probe,ensure probe synthesis and retention of bimodal properties.Then design the nano delivery system,polyglycidyl methacrylate was synthesized by atom transfer radical polymerization,and the hydrogen peroxide sensitive block polymer PGMA-PEG was synthesized by utilizing the characteristics of active oxygen response in atherosclerosis.Then modify the target molecule that targets macrophages to inhibit the migration factor ISO-1 and the anti-atherosclerotic drug Simvastatin（Sim）,The amphiphilic polymer PGMA-PEG-ISO-1-Sim released by the hydrogen peroxide sensitive control probe was obtained to form micelles,and the probe was coated to obtain PGMA-PEG-ISO-1-Sim@FC.We encapsulated the bimodal probe in a hydrogen peroxide-sensitive amphiphilic polymer to achieve the preparation of smart responsive bimodal probe nanomicelles.The delivery system was tested and characterized,and polymer synthesis was confirmed by nuclear magnetic hydrogen spectroscopy（¹H-NMR）,nuclear magnetic carbon spectroscopy(¹³C-NMR),and infrared（FT-IR）.The size and spherical morphology of the nanoparticles were determined using dynamic light scattering（DLS）and transmission electron microscopy（TEM）.The change of the imaging ability of the probe was determined using a vibrating sample magnetometer and a fluorescence spectrum.By simulating the hydrogen peroxide concentration at the atherosclerotic plaque,the details and imaging effects of nano-delivery on this stimulus were obtained.In order to confirm the potential of the nanoparticle biological application,we performed material hemolysis experiments,and tested the cytotoxicity using the MTT method,and obtained ideal experimental results.The uptake of nanoparticles in macrophages and endothelial cells was observed by a confocal microscope,and the effect of probe fluorescence imaging was observed.The nanoprobe was then applied to ApoE^-/-atherosclerotic mouse models to detect the effects of nuclear magnetic resonance imaging（MRI）and in vivo and in vitro fluorescence imaging.Finally,the safety of the experimental mice was tested to confirm the safety of the nanoprobe.Based on the above experimental results,it is confirmed that the nanoprobe has excellent targeting ability and detection effect.In addition,the drug release of micelles was obtained by simulating the hydrogen peroxide concentration at the atherosclerotic plaque.The cytotoxicity of drug-loaded micelles was obtained by MTT method.The rabbit carotid artery was stimulated to produce atherosclerosis.The therapeutic effect of nanometer drug-loaded micelles was detected using Doppler color Doppler ultrasound;the therapeutic effect was analyzed by analyzing plaques and sections of the carotid artery after stimulation.Finally,safety tests were performed on experimental animals to confirm the safety of the nanomedicine-loaded micelles.It was confirmed that the nano-micelle has excellent targeting ability and therapeutic effect.In addition,lecithin,cholesterol,apolipoprotein A1 and PEG phosphatidylserine were used to synthesize recombinant high-density lipoprotein（rsHDL）.The synthetic dual-mode probe was coated to obtain the diagnostic and therapeutic nanoparticle rsHDL@FC.Then the physical and chemical characterization of the nano-system is carried out concurrent target ability test,imaging ability test,treatment ability test,etc.This article aims at atherosclerosis,and synthesizes two different types of nanoparticles with diagnostic and therapeutic functions,and provides a new idea for the design of integrated drug-loaded nanoparticles for diagnosis and treatment,and hopes to play a role in the diagnosis and treatment of atherosclerotic diseases.