Synthesis Of H₂O₂-responsive Nano Carrier And The Study In Atherosclerosis

In cardiovascular diseases,the mortality caused by atherosclerosis is increasing.How to achieve prevention and treatment in the early stages of the disease has always been the focus of research.Researchers have achieved this by modifying various imaging,targeting,therapeutic agents and diagnostics on the surface of nanoparticles.Among them,liposomes are more promising materials because of their excellent biocompatibility,low immunogenicity and other properties.The nano drug delivery system achieves the effect of accumulating in the patient through passive and active targeting mechanisms to achieve imaging or therapeutic purposes.At the plaques of atherosclerosis,there are various cells such as monocytes,macrophages and foam cells.Targeting the most influential cells is a very promising direction.Compared with cancer and other diseases,there is no obvious p H difference in atherosclerotic plaque,but there is a certain concentration of hydrogen peroxide and pressure,so the use of its special pathological environment is the focus of the disease diagnosis and treatment process.In this paper,based on the response of H₂O₂ two nano carriers were designed and synthesized.First,we synthesized polyitaconic acid which with good biocompatibility.However,the limited solvent compatibility of polyitanic acid has become a problem that needs to be overcome in experiments.Therefore,by modifying a certain proportion of PEG on the polymer main chain,the solubility of the polymer is improved while enhancing the circulation ability in the body.In order to make the polymer have the therapeutic function of the dual-function nanoparticles and respond to the stimulation condition of the hydrogen peroxide concentration at the plaque,we use the amino group of aminophenylboronic acid to react with the carboxyl group of the polyitaconic acid to form an amide bond,and use this as a bridge.The anti-inflammatory drug rutin is attached to the polymer.Finally,in order to make the polymer have a dual function of dual function: imaging,we prepared environmentally friendly non-toxic carbon fluorescent quantum dots by microwave method and adsorbed them on the outer layer of the polymer by electrostatic adsorption.So far,the dual-function nanoparticles with hydrogen peroxide stimulating responsiveness were synthesized.We confirmed the structure of the polymer by basic characterizations.The polymer exhibits low biotoxicity and good cell uptake capacity and is an excellent biomaterial.Next part of the job is to design and synthesize multifunctional liposomes.First,based on the requirements of hydrogen peroxide stimulation response,we synthesized a block polymer of polyethylene glycol polypropylene sulfide and coated it with rhodamine B as a drug model,confirming that the polymer has the ability to coat the drug and H₂O₂-responsive.Subsequently,we were coated with simvastatin and FITC-SiO₂@Fe₃O₄ bimodal probes.Then,we chose one of the cell membrane components: phosphatidylserine to coat the micelles.The phospholipid is called a "eat me" signal because of its ability to be specifically recognized by macrophages.Therefore,we separately coated the drug and the bimodal probe with phosphatidylserine by a thin film dispersion method.The micelles produce liposomes with stimuli responsiveness.The resulting liposomes show good biological properties and meet the requirements as biomedical materials.In conclusion,based on the hydrogen peroxide stimulation response,nano-micelles and liposomes with different structures were prepared,which provided a novel idea for atherosclerosis.