Manganese Oxide Functional Nanomaterials Used To Inhibit Endothelial Inflammation And Prevent Atherosclerosis

Atherosclerosis?AS?is a chronic inflammatory disease that accumulates on the walls of arterial blood vessels similar to yellow atheromatous lipid plaques.Studies show that in areas prone to AS lesions,the blood flow pattern changes from laminar to turbulent,generating abnormal shear stress,increasing the levels of proinflammatory factors in vascular endothelial cells,thereby activating multiple inflammatory signaling pathways,leading to blood vessels Redox imbalance in endothelial cells,oxidative modification of proteins,and changes in biological morphology,structure,and functional state eventually lead to plaque formation.In recent years,a variety of acute cardiovascular and cerebrovascular events caused by AS have been increasing year by year,and have become the first major disease that threatens human health.At this stage,it is a pivotal problem to effectively treat AS in the cardiovascular field.At present,the methods commonly used for the prevention and treatment of AS are mainly drug treatment?blood lipid regulation,antiplatelet,anticoagulation,etc.?and surgery.However,the above methods have disadvantages.For example,nicotinic acid and statins can easily cause side effects such as abnormal liver function,gastrointestinal symptoms,and cataracts.The drugs lack targetedness and specificity.Surgical treatment is expensive and It is easy to relapse and cannot prevent the development of plaque.Therefore,how to treat atherosclerosis safely and effectively is still a difficult point in the field of cardiovascular research.In recent years,the emerging nanotechnology has provided an opportunity to solve the above problems,and many nanomaterial-based treatment methods have received extensive attention and research.Nanomaterials have high spatiotemporal resolution and have become a powerful tool for regulating protein function.It is expected to develop a safe,efficient,specific,small toxic and side effect,and biocompatible strategy at the molecular level for precision Regulate cell signaling pathways to prevent AS plaque formation.Studies have shown that high laminar-induced high shear stress and anti-oxidation effects can play an anti-AS role through corresponding signal pathways.However,the laminar flow simulants and antioxidant drugs that have been developed currently have defects such as large toxic and side effects,poor targeting,and low bioavailability.With the goal of accurately inhibiting inflammatory signaling pathways in vivo,we turned our attention to manganese oxide nanomaterials.Studies have shown that manganese oxide nanomaterials have great application prospects in the diagnosis and treatment of diseases due to their excellent physical and chemical properties,such as electromagnetic,photoelectric,and catalytic properties.MnO₂ nanoparticles can be decomposed into Mn²⁺in plaque microenvironment to simulate laminar flow effect.And Mn₃O₄ is an antioxidant,which can reverse the thiol nitrosation of proteins and play an anti-inflammatory effect.Therefore,manganese oxide nanomaterials are expected to provide a powerful tool for the prevention and treatment of AS.In view of this,here the use of manganese oxide nanomaterials,which simultaneously replaced biological nanotube cell membranes,functionalized modification of peptide peptides,based on the activation of integrin by Mn²⁺and the antioxidant properties of Mn₃O₄,has achieved accurate signal pathways Decomposes and improves the ability to contract plaques,helping to provide effective anti-inflammatory and anti-oxidant treatment for atherosclerosis:1.We designed a biomimetic high-performance laminar flow simulator for the anti-inflammatory and atherosclerotic protective effects of the areas of the blood vessels exposed to steady-flow-induced laminar shear stress?LSS?.It is a reductively separable bovine serum albumin?BSA?-MnO₂ nanoparticle encased in a membrane of endothelial cells?EC?for the treatment of AS.Thanks to surface functionalization,our MnO₂ nanoparticles are endowed with homologous targeting and immune escape capabilities,greatly improving their ability to accumulate and retain plaque in the body.Once inside the plaque,the MnO₂ in the EC-BSA-MnO₂ nanoparticles will react with a large number of plaque metabolites?H₂O₂ and H⁺?,releasing Mn²⁺in situ under controlled control,thus effectively inhibiting integrin-coupled inflammatory signaling pathways.In addition,the accumulation of macrophages and plaque formation in the aorta of apolipoprotein E deficiency?ApoE^-/^-?mice on a high-fat diet was significantly reduced,with no significant adverse effects.Therefore,the results of this study indicate that EC-BSA-MnO₂,a biomimetic nanoparticle with reductive separation,is a safe and effective tool to delay atherosclerosis.2.After nitrogenization of nuclear transcription factor KLF4,its transcriptional activity and nuclear localization would be reduced,which would lead to impaired vascular endothelial function.Therefore,we constructed a functionalized manganese tetroxide?Mn₃O₄?nanomaterial to precisely and efficiently regulate endothelial inflammation.This material is composed of flower-like Mn₃O₄ nanoparticles and vascular endothelial cell targeting peptide?VHPK?.NH₂-on VHPK and Mn₃O₄ nanoparticle-carboxyl are connected together by reacting to form amide bonds.The results showed that the VHPK-Mn₃O₄ synthesized by us not only has good biocompatibility,but also can specifically target vascular endothelial cells.At the cellular level,VHPK-Mn₃O₄ can effectively reverse the nitrogenation of KLF4 induced by GSNO through antioxidant action,enhance its nuclear localization and transcriptional translation ability,so as to increase the level of target protein eNOS,with obvious anti-inflammatory effect,and it is expected to achieve effective intervention and treatment of atherosclerotic plaque in vivo in the later study.