| Ischemic stroke is one of the most common cardiovascular and cerebrovascular diseases at present,threatening human health.Cells in brain cannot get oxygen and nutrients in time during cerebral ischemia,which could produce a large number of free radicals and cause inflammatory reactions.However,inflammatory reactions in turn promote the production of more free radicals,obviously destroy the cell structure,and cause damage cascade reaction.Therefore,in recent years,scholars at home and abroad began to focus on drugs that can inhibit inflammatory reaction and scavenge free radicals to treat ischemic stroke.Micro-and nanomotors(MNMs)can convert chemical or external energy into mechanical motion to complete complex tasks.Because of its active motion ability,cargo transportation and effective penetration ability,MNMs has shown excellent potential in various biomedical applications.At the same time,recent studies have found that hydrogen therapy is a new and promising treatment strategy,and hydrogen molecules can specifically remove highly cytotoxic reactive oxygen species,including ·OH and ONOO-,but also can preserve other active oxygen required by normal signals,which is very beneficial to antioxidation and anti-inflammation.In this study,hydrogen-powered microswimmers(HPMs)were fabricated by asymmetrically coating magnesium particles with biodegradable polymer polylactic acid-glycolic acid copolymer(PLGA).The hydrogen generated locally from HPMs by consuming water is not only used as a propellant for exercise,but also as an active ingredient for scavenging active oxygen and inflammation.HPMs were planned to be injected into the tricorn of MCAO rats precisely under the guidance of brain stereotactic apparatus,with antioxidant and anti-inflammatory treatment on cerebral ischemia-reperfusion injury in vivo.Chapter 1:Preparation of HPMs and motion research.The asymmetrically spherical structure of HPMs was successfully prepared by spin coating method.SEM and EDX results showed that magnesium element distribution from magnesium particles and carbon and oxygen distribution from PLGA shell were observed in microswimmers,which proved the successful formation of Janus structure.Due to the continuous detachment of the produced hydrogen,the speed of the microswimmers is up to 51.1 ?m s-1 in artificial cerebrospinal fluid(ACSF)and 61.12 ?m s-1 in phosphate buffer saline(PBS),resulting in active H2 delivery that allows for enhanced extracellular and intracellular reducibility.Chapter 2:Study of HPMs on the treatment of LPS-induced RAW264.7 cells inflammation model.The RAW264.7 cells inflammation model induced by LPS.Cell viability test and hemolysis test showed that SiO2@PLGA,HPMs and magnesium particles were not cytotoxic.At the same time,magnesium particles and HPMs have the ability of scavenging ROS by detecting DCFH-DA concentration and Cellrox staining.Finally,the results of qPCR and ELISA showed that magnesium particles and HPMs could reduce the mRNA level and concentration of inflammatory factors IL-1?,TNF-? and IL-6 in LPS-induced RAW264.7 cells.Chapter 3:Application of HPMs in precise treatment of MCAO rats.With the help of stereotactic instrument,HPMs was accurately injected into the lateral ventricle of MCAO rats.By scavenging ROS and inflammation,the infarct volume of MCAO rats was significantly reduced,the ability of spatial learning and memory was improved,and the side effects were minimal,which proved the effective role of HPMs in anti-ischemic stroke.To sum up,this study has developed high-performance medical polymer materials with good biocompatibility and ROS scavenging ability,which provides a broad prospect for clinical treatment of acute ischemic stroke or other oxidative stress-related diseases.Biodegradable micromotor has great potential for minimally invasive targeted therapy because of its small size,multiple functions and wide applications. |
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