| With the change of modern living habits and the acceleration of the pace of life,atherosclerosis and other diseases,which were originally prone to the elderly,now appear gradually younger.As a disease with extremely high morbidity and mortality in the world,atherosclerosis has brought great troubles to People’s Daily life.This paper first describes the causes of atherosclerosis,the development of the disease,as well as the traditional treatment means,hope for atherosclerosis for the treatment of some inspiration.The rise of nano-drug delivery system has brought new hope to the treatment of atherosclerosis.In order to achieve the purpose of precision treatment,nano-drug delivery system has developed a variety of different stimulus response programs,which plays an extremely important role in the treatment of atherosclerosis.Although the morbidity and mortality of atherosclerosis are high,the progression of atherosclerosis is often slow,which makes the diagnosis of atherosclerosis extremely important.This paper briefly introduces the relevant diagnostic methods.In order to realize the combination of diagnosis and treatment,this paper designed an intelligent and responsive diagnostic and treatment integrated nanoparticle based on the modifiable characteristics of nanocarriers,in order to provide a feasible scheme for the diagnosis and treatment of atherosclerosis.In this paper,P（TFEMA-co-GMA）was synthesized by atom transfer radical polymerization copolymerization,and modified amino group was introduced by ethylenediamine ring opening.The amino group reacted with m PEG-CHO to obtain p H response and F signal responsive material P（TFEMA-co-GMA-EDA）-g-PEG.The introduction of PEG can significantly improve the biocompatibility of the material and prolong the circulation time in vivo.In this paper,NMR and IR were used to prove the successful preparation of the material.Furthermore,DLS and UV were used to detect the effects of different PEG grafting rates on the particle size,Zeta potential,drug loading rate and encapsulation rate of simvastatin supported micelles.The optimal grafting rate of PEG was selected as 20%.The subsequent modification can actively target the small molecule ligand（ISO-1）and 4-o-phenylenediamine-1,8-naphthalene dimethylanhydride fluorophore group（PDNA）of macrophages in atherosclerosis patients for the enrichment of micelles in patients and the monitoring of micelle distribution in vivo.The combination of active targeting and passive targeting was realized by removing the PEG shell to improve the performance of DLS,TEM,drug release behavior,p H response behavior,fluorescence test and other experiments.In order to further verify the biological role of drug-carrying micelles,in vitro hemolysis,in vitro cytotoxicity and in vitro cell uptake experiments were carried out to prove their good biocompatibility,targeted therapeutic ability and fluorescence imaging ability.Use of Apo E-/-knockout mice and New Zealand white rabbit carotid artery intervention in animal model to study the drug micelle drug metabolism in the body,the body of experimental treatment,safety assessment in the body,such as testing,the results show that drug micelle in the body have good biocompatibility and good treatment effect,in the aspect of atherosclerosis has better clinical effect.A drug delivery system that responds to the acidic environment of atherosclerosis and specifically binds to macrophages was designed and prepared.In this system,polyethylene glycol b-polymethyl methacrylate（PEG-b-PDMAEMA）was synthesized by ATRP polymerization.PEG formed hydrophilic end,DMEMA formed hydrophobic end,and simvastatin was loaded to form drug-loading micelles（Sim MC）.The Sim MC is then coated by phosphatidylserine（PS）to form PS@Sim MC.The drug delivery system has p H response and can target inflammatory macrophages to achieve specific release in atherosclerosis to improve therapeutic effect.The results show that PS@Sim MC is a promising intelligent response liposome for atherosclerosis. |
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