Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammat...Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.展开更多
Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated wit...Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.展开更多
基金supported by National Key R&D Program of China (No.2022YFC3501700)National Natural Science Foundation of China (No.82274059)+3 种基金Naval Military Medical University,Far East Talent Project (No.SL-33)Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (No.CPA-Z05-ZC-2024-003)Shanghai Oriental Talent Plan Youth Program (formerly Shanghai Young Top-Notch Talent) (2023)the Baoshan District Medical Key Science (Specialty) and Specialty Brand Construction Project (No.BSZK-2023-A12)。
文摘Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.
基金financial support provided by the National Natural Science Foundation of Shanghai(No.20ZR1420000)Shanghai Shen Kang Center Research Physician Training Program on Innovation and Translation Capabilities(No.SHDC2022CRS051)Three-Year Action Plan for Improving Clinical Research Capacity of International Peace Maternal and Child Health Hospital,Shanghai Jiao Tong University School of Medicine(No.IPMCH2022CR1-05).
文摘Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.
