Preparation And Application Of Micro-nano Motors For Cardiovascular Disease Treatment

Cardiovascular diseases,such as thrombosis and atherosclerosis(AS),pose a serious threat to human health.The emergence of micro/nanomotors with the ability to convert external energy into autonomous movement has made it possible to break through the limitations of traditional nano drug delivery systems in the treatment process.Based on this,this paper designs and prepares a series of micro/nanomotors for the treatment of cardiovascular diseases,the specific content is as follows:1.Vein thrombosis is one of the most serious types of cardiovascular disease.During treatment,due to the excessive blood flow rate,the drug utilization rate at the thrombus site is low and the thrombolysis efficiency is poor.In this study,bowl-like silica drug-loaded nanomotor driven by nitric oxide(NO)was designed to target the thrombus surface by modifying with arginine-glycine-aspartate peptide(RGD)and simultaneously loading with L-arginine and drug urokinase(UK)using a mesopore structure.L-arginine can react with excessive reactive oxygen species(ROS)in the thrombus microenvironment to produce NO,thus promoting the movement of nanomotor to improve the retention efficiency and utilization rate of drugs in the thrombus site,and at the same time achieve the effect of eliminating ROS and reducing the oxidative stress of inflammatory endothelial cells and activated platelets.The loaded UK can dissolve thrombus quickly.It is worth mentioning that NO can not only be used as a power source of nanomotor to improve the penetration ability of nanomotor in the thrombosis site and improve drug retention rate,but also can be used as a therapeutic agent to stimulate the growth of endothelial cells and reduce vascular injury.This therapeutic agent based on micro/nanomotor technology is expected to provide support for future research on thrombus treatment.2.AS is the pathological basis of thrombosis.Currently,the difficulty in the treatment of AS lies in its complex pathogenesis,which involves the ablation of inflammatory macrophages,repair of vascular endothelial injury and anti-tissue proliferation.Therefore,a multifunctional mesoporous/macroporous tubular micromotor driven by near-infrared(NIR)light is proposed in this paper,which can rapidly target blood vessel damage and release different drugs.The motion effect of the micromotor can promote its own penetration into the plaque site,and the thermal effect generated by NIR light can realize the photothermal ablation of inflammatory macrophages.In addition,micromotors can rapidly release vascular endothelial growth factor(VEGF)for endothelialization(about 4 h)and slowly release anti-proliferative paclitaxel(PTX)(more than 20 d)to achieve synergism in the treatment of AS.The results of in vivo and in vitro experiments show that the micromotor has a good therapeutic effect on AS.This kind of drug-loaded micro/nano motor technology with complex pore structure will lead to more potential disease treatment platform.3.In addition to the late treatment of AS,it is also critical to effectively intervene and regulate the microenvironment of early AS to inhibit the progression of the disease.In this paper,we also attempted to construct a dual-driven nanomotor sensitive to AS microenvironment and NIR light by covalent binding and self-assembly of β-cyclodextrin and L-arginine nanoparticles,and further in-situ fixation of gold nanoparticles(Au NPs).The experimental results show that the near-infrared light radiation can not only provide the driving force of the nanomotor movement,but also can ablate the inflammatory macrophages through the photothermal effect.In this process,L-arginine can participate in the consumption of ROS in the inflammatory site,delaying the process of AS,and the release of NO can also be used AS another driving force of nanomotor and therapeutic agent for endothelial repair in AS site.The presence of β-cyclodextrin can promote the clearance of cholesterol in foam cells.The two driving modes of the nanomotor synergically promote its aggregation and penetration in the plaque,thus promoting its therapeutic effect.The nanomotor can regulate many aspects of the process of AS,including ablation of inflammatory cells,reduction of systemic oxidative stress,repair of vascular endothelium and removal of lipid plaques,and is expected to become a potential active drug delivery system for the treatment of AS.