The blood–brain barrier: Structure, regulation and drug delivery

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates pharmacotherapy for CNS disorders as most chemical drugs biopharmaceuticals have been impeded to enter brain. Insufficient drug delivery into brain leads low therapeutic efficacy well aggravated side effects due accumulation other organs tissues. Recent breakthrough materials science nanotechnology provides library advanced with customized structure property serving powerful toolkit targeted delivery. In-depth research field anatomical pathological study on further facilitates development brain-targeted strategies enhanced crossing. In this review, physiological different cells contributing are summarized. Various emerging permeability regulation crossing including passive transcytosis, intranasal administration, ligands conjugation, coating, stimuli-triggered disruption, overcome obstacle highlighted. Versatile systems ranging organic, inorganic, biologics-derived their synthesis procedures unique physio-chemical properties summarized analyzed. This review aims provide an up-to-date comprehensive guideline researchers diverse fields, offering perspectives system.

Language: Английский

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Highly bioactive zeolitic imidazolate framework-8–capped nanotherapeutics for efficient reversal of reperfusion-induced injury in ischemic stroke

Science Advances, Journal Year: 2020, Volume and Issue: 6(12)

Published: March 18, 2020

Rational design of potent antioxidative agent with high biocompatibility is urgently needed to treat ischemic reperfusion-induced ROS-mediated cerebrovascular and neural injury during ischemia strokes. Here, we demonstrate an in situ synthetic strategy bioactive zeolitic imidazolate framework-8–capped ceria nanoparticles (CeO2@ZIF-8 NPs) achieve enhanced catalytic activities improved stroke therapeutic efficacy. This nanosystem exhibits prolonged blood circulation time, reduced clearance rate, BBB penetration ability, brain accumulation, where it effectively inhibits the lipid peroxidation tissues middle cerebral artery occlusion mice reduces oxidative damage apoptosis neurons tissue. CeO2@ZIF-8 also suppresses inflammation- immune response–induced by suppressing activation astrocytes secretion proinflammatory cytokines, thus achieving satisfactory prevention treatment neuroprotective therapy. study sheds light on action mechanisms ZIF-8–capped nanomedicine against stroke.

Language: Английский

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Macrophage‐Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke

Advanced Science, Journal Year: 2021, Volume and Issue: 8(20)

Published: Aug. 26, 2021

Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which due to lack of comprehensive neuroprotective effects. Herein, macrophage-disguised honeycomb manganese dioxide (MnO2 ) nanosphere loaded with fingolimod (FTY) developed salvage penumbra. In particular, biomimetic nanoparticles can accumulate actively damaged brain via macrophage-membrane protein-mediated recognition cell adhesion molecules overexpressed vascular endothelium. MnO2 consume excess hydrogen peroxide (H2 O2 and convert it into desiderated oxygen (O2 ), be decomposed acidic lysosome for cargo release, so as reduce oxidative stress promote transition M1 microglia M2 type, eventually reversing proinflammatory microenvironment reinforcing neuron. This nanomedicine raises new strategy multitargeted combined treatment

Language: Английский

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Mitochondria-targeted TPP-MoS2 with dual enzyme activity provides efficient neuroprotection through M1/M2 microglial polarization in an Alzheimer's disease model

Biomaterials, Journal Year: 2019, Volume and Issue: 232, P. 119752 - 119752

Published: Dec. 30, 2019

Language: Английский

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Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Journal of Controlled Release, Journal Year: 2020, Volume and Issue: 327, P. 641 - 666

Published: Sept. 8, 2020

Language: Английский

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Bioactive Nanoenzyme Reverses Oxidative Damage and Endoplasmic Reticulum Stress in Neurons under Ischemic Stroke

ACS Nano, Journal Year: 2021, Volume and Issue: 16(1), P. 431 - 452

Published: Dec. 27, 2021

Designing translational antioxidative agents that could scavenge free radicals produced during reperfusion in brain ischemia stroke and alleviate neurologic damage is the main objective for ischemic treatment. Herein, we explored simply synthesized a biomimic Mn3O4 nanoenzyme (HSA-Mn3O4) to constrain reperfusion-induced nervous system injury. This nanosystem exhibits reduced levels of inflammation prolonged circulation time potent ROS scavenging activities. As expected, HSA-Mn3O4 effectively inhibits oxygen glucose deprivation-mediated cell apoptosis endoplasmic reticulum stress demonstrates neuroprotective capacity against injury tissue. Furthermore, releases Mn ions promotes increase superoxide dismutase 2 activity. Therefore, tissue by restraining vivo. Taken together, this study not only sheds light on design nanomedicine but also reveals action mechanisms

Language: Английский

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A Thrombin‐Activated Peptide‐Templated Nanozyme for Remedying Ischemic Stroke via Thrombolytic and Neuroprotective Actions

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(10)

Published: Feb. 2, 2023

Ischemic stroke (IS) is one of the most common causes disability and death. Thrombolysis neuroprotection are two current major therapeutic strategies to overcome ischemic reperfusion damage. In this work, a novel peptide-templated manganese dioxide nanozyme (PNzyme/MnO

Language: Английский

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Targeted Treatment of Ischemic Stroke by Bioactive Nanoparticle-Derived Reactive Oxygen Species Responsive and Inflammation-Resolving Nanotherapies

ACS Nano, Journal Year: 2021, Volume and Issue: 15(10), P. 16076 - 16094

Published: Oct. 4, 2021

Stroke is a primary cause of death and disability worldwide, while effective safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies ischemic stroke, which are engineered from pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating radical-scavenging compound (Tempol) hydrogen-peroxide-eliminating moiety phenylboronic acid pinacol ester (PBAP) on β-cyclodextrin. Of note, combined functional moieties Tempol PBAP β-cyclodextrin contribute antioxidative anti-inflammatory activities TPCD. Cellularly, TPCD nanoparticles (i.e., NPs) reduced oxygen-glucose deprivation-induced overproduction oxidative mediators, increased antioxidant enzyme expression, suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, NPs could efficiently accumulate at the cerebral injury site mice with middle artery occlusion (MCAO), showing considerable distribution in cells relevant pathogenesis stroke. Therapeutically, significantly decreased infarct volume accelerated recovery neurological function MCAO mice. Mechanistically, efficacy achieved antioxidative, anti-inflammatory, antiapoptotic effects. Furthermore, can reactive oxygen species labile nanovehicle load triggerably release an inflammation-resolving peptide Ac2-26, giving rise nanotherapy ATPCD NP). Compared NP, NP demonstrated notably enhanced vivo efficacies, largely resulting additional activity. Consequently, NP-derived nanomedicines further promising targeted therapies stroke other inflammation-associated cerebrovascular diseases.

Language: Английский

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Engineered Nanoerythrocytes Alleviate Central Nervous System Inflammation by Regulating the Polarization of Inflammatory Microglia

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(27)

Published: April 28, 2022

Microglial polarization is one of the most promising therapeutic strategies for multiple central nervous system (CNS) disorders. However, safe, effective, and controllable microglial regulation still faces formidable challenges. Although some anti-inflammatory factors promote microglia polarization, their short half-life, high cost, unpredictable in vivo behavior, complex delivery operations, hamper clinical application. Here, inspired by natural microhemorrhage cleaning mechanism, an MG1 peptide RVG29 engineered nanoerythrocyte (NEMR) that can reprogram are developed from classical M1 toward alternative M2 inducing heme oxygenase-1 (HO-1), stimulating Notch1/Hes1/Stat3 signaling, further inhibiting NF-κB p65 translocation. Moreover, carbon monoxide (CO) bilirubin produced endogenous metabolism reinforces effect. In middle cerebral artery occlusion experimental autoimmune encephalomyelitis models, a satisfactory prognosis achieved, with precise inflammatory lesion sites, increased expression factors, reduced blood-brain barrier permeability, as well promotion neurogenesis functional recovery. Furthermore, NEMR be integrated agents, which facilitates drug to enhance effects. Hence, nanoerythrocytes, feasible, efficient, practical tool, provides new strategy rebalancing immune environment CNS

Language: Английский

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Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 17, 2023

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide. However, current drug therapeutics compromised by narrow therapeutic windows, unsatisfactory thrombolysis effects, severe bleeding events, high recurrence rates. In this study, we exploit a self-propelling nano-penetrator with fuel loading controllable motion features, which is molecularly co-assembled using photothermal photosensitizer (DiR) photothermal-activable NO donor (BNN6). The precisely engineered BNN6-DiR pair shows distinct advantages in terms productivity autonomous under laser irradiation. animal models artery/vein thrombosis acute ischemic stroke, self-fueled enables self-navigated thrombus-homing accumulation, self-propelled clot deep penetration, fluorescence image-guided photothermal/mechanical thrombolysis, NO-mediated prevention stroke salvage. As expected, displayed favorable outcomes without risk compared to clinically available thrombolytic drug. This study offers facile, safe, effective nonpharmaceutical modality towards clinical treatment stroke.

Language: Английский

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