{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:30:14Z","timestamp":1789684214823,"version":"4.0.1"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient\u2019s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapies.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050757","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T06:13:45Z","timestamp":1621491225000},"page":"757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["New Approaches in Nanomedicine for Ischemic Stroke"],"prefix":"10.3390","volume":"13","author":[{"given":"Clara","family":"Correa-Paz","sequence":"first","affiliation":[{"name":"Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"da Silva-Candal","sequence":"additional","affiliation":[{"name":"Neurology Service, University Hospital Complex of A Coru\u00f1a, A Coru\u00f1a Biomedical Research Institute, 15006 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Polo","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Qu\u00edmica Biol\u00f3xica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15782 Santiago, Spain"},{"name":"Grupo de F\u00edsica de Coloides y Pol\u00edmeros, Departamento de F\u00edsica de Part\u00edculas, Universidade de Santiago de Compostela, 15782 Santiago, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Parcq","sequence":"additional","affiliation":[{"name":"Op2Lysis SAS, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Vivien","sequence":"additional","affiliation":[{"name":"UNICAEN, INSERM U1237, Etablissement Fran\u00e7ais du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, 14000 Caen, France"},{"name":"Department of clinical research, Caen-Normandie University Hospital, CHU, Avenue de la c\u00f4te de Nacre, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-5201","authenticated-orcid":false,"given":"Dusica","family":"Maysinger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics, McGill University, Montr\u00e9al, QC H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Pelaz","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Qu\u00edmica Biol\u00f3xica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15782 Santiago, Spain"},{"name":"Grupo de F\u00edsica de Coloides y Pol\u00edmeros, Departamento de Qu\u00edmica Inorg\u00e1nica, Universidade de Santiago de Compostela, 15782 Santiago, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1039","authenticated-orcid":false,"given":"Francisco","family":"Campos","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association\/American Stroke Association","volume":"50","author":"Powers","year":"2019","journal-title":"Stroke"},{"key":"ref_2","first-page":"1","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","first-page":"1","article-title":"Vectorized nanodelivery systems for ischemic stroke: A concept and a need","volume":"15","author":"Argibay","year":"2017","journal-title":"J. Nanobiotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nm1735","article-title":"A new penumbra: Transitioning from injury into repair after stroke","volume":"14","author":"Lo","year":"2008","journal-title":"Nat. Med."},{"key":"ref_5","first-page":"S7","article-title":"Targeting the Ischemic Penumbra","volume":"42","author":"Campos","year":"2010","journal-title":"Stroke"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41582-018-0002-2","article-title":"Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke","volume":"14","author":"Baron","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1001\/jama.2020.23523","article-title":"Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke: The devt randomized clinical trial","volume":"325","author":"Zi","year":"2021","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S1474-4422(16)00114-9","article-title":"Neuroprotection in acute stroke: Targeting excitotoxicity, oxidative and nitrosative stress, and inflammation","volume":"15","author":"Chamorro","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3389\/fneur.2019.00332","article-title":"Cell-Based Therapies for Stroke: Promising Solution or Dead End? Mesenchymal Stem Cells and Comorbidities in Preclinical Stroke Research","volume":"10","author":"Diekhorst","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ijpharm.2018.01.016","article-title":"Recent trends of nanomedicinal approaches in clinics","volume":"538","author":"Dilnawaz","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1021\/acsnano.6b06040","article-title":"Diverse Applications of Nanomedicine","volume":"11","author":"Pelaz","year":"2017","journal-title":"ACS Nano"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.7150\/thno.11835","article-title":"Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging","volume":"5","author":"Belliere","year":"2015","journal-title":"Theranostics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3389\/fncel.2014.00389","article-title":"Molecular magnetic resonance imaging of brain-immune interactions","volume":"8","author":"Gauberti","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.7150\/thno.22662","article-title":"Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System","volume":"8","author":"Gauberti","year":"2018","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/mrm.20342","article-title":"Sizing it up: Cellular MRI using micron-sized iron oxide particles","volume":"53","author":"Shapiro","year":"2005","journal-title":"Magn. Reson. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.7150\/thno.24128","article-title":"In vivo imaging biomarkers of neuroinflammation in the development and assessment of stroke therapies\u2014towards clinical translation","volume":"8","author":"Zinnhardt","year":"2018","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: From mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1161\/STROKEAHA.111.000544","article-title":"Ultra-Sensitive Molecular MRI of Vascular Cell Adhesion Molecule-1 Reveals a Dynamic Inflammatory Penumbra After Strokes","volume":"44","author":"Gauberti","year":"2013","journal-title":"Stroke"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s11307-013-0617-z","article-title":"Mri of icam-1 upregulation after stroke: The importance of choosing the appropriate target-specific particulate contrast agent","volume":"15","author":"Deddens","year":"2013","journal-title":"Mol. Imaging Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/brain\/aww260","article-title":"Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack","volume":"140","author":"Quenault","year":"2017","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1161\/ATVBAHA.107.145466","article-title":"Magnetic Resonance Imaging of Endothelial Adhesion Molecules in Mouse Atherosclerosis Using Dual-Targeted Microparticles of Iron Oxide","volume":"28","author":"McAteer","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.7150\/thno.11679","article-title":"Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles","volume":"5","author":"Kim","year":"2015","journal-title":"Theranostics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14254","DOI":"10.1038\/ncomms14254","article-title":"Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI","volume":"8","author":"Aljabali","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics-2019 update: A report from the american heart association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"Chapin","year":"2015","journal-title":"Blood Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2466","DOI":"10.1038\/cddis.2016.279","article-title":"Tissue-type plasminogen activator controls neuronal death by raising surface dynamics of extrasynaptic NMDA receptors","volume":"7","author":"Lesept","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1161\/STROKEAHA.110.592535","article-title":"Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: Real-world experience and a call for action","volume":"41","author":"Bhatia","year":"2010","journal-title":"Stroke"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.csbj.2019.06.023","article-title":"Structural Biology and Protein Engineering of Thrombolytics","volume":"17","author":"Mican","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_29","first-page":"e28","article-title":"Heart Disease and Stroke Statistics--2014 Update: A Report from the American Heart Association","volume":"129","author":"Go","year":"2013","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1001\/jama.2015.13767","article-title":"Endovascular thrombectomy for acute ischemic stroke: A meta-analysis","volume":"314","author":"Badhiwala","year":"2015","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1056\/NEJMoa1716405","article-title":"Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke","volume":"378","author":"Campbell","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1161\/STROKEAHA.118.022744","article-title":"Recent Advances in Nanomedicine for Ischemic and Hemorrhagic Stroke","volume":"50","author":"Bonnard","year":"2019","journal-title":"Stroke"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/17425247.2018.1384464","article-title":"Tissue plasminogen activator-based nanothrombolysis for ischemic stroke","volume":"15","author":"Liu","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1055\/s-0038-1653802","article-title":"Thrombolytic Treatment with Tissue-type Plasminogen Activator (t-PA) Containing Liposomes in Rabbits: A Comparison with Free t-PA","volume":"73","author":"Heeremans","year":"1995","journal-title":"Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7746","DOI":"10.1021\/nn5029955","article-title":"Acceleration of Tissue Plasminogen Activator-Mediated Thrombolysis by Magnetically Powered Nanomotors","volume":"8","author":"Cheng","year":"2014","journal-title":"ACS Nano"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11239-010-0450-z","article-title":"Construction of thrombus-targeted microbubbles carrying tissue plasminogen activator and their in vitro thrombolysis efficacy: A primary research","volume":"30","author":"Hua","year":"2010","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11239-014-1071-8","article-title":"In vivo thrombolysis with targeted microbubbles loading tissue plasminogen activator in a rabbit femoral artery thrombus model","volume":"38","author":"Hua","year":"2014","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1088\/1361-6560\/62\/2\/517","article-title":"In vitro thrombolytic efficacy of echogenic liposomes loaded with tissue plasminogen activator and octafluoropropane gas","volume":"62","author":"Shekhar","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/jbm.a.32234","article-title":"The t-pa-encapsulated plga nanoparticles shelled with cs or cs-grgd alter both permeation through and dissolving patterns of blood clots compared with t-pa solution: An in vitro thrombolysis study","volume":"91","author":"Wang","year":"2009","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.biomaterials.2007.09.027","article-title":"Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (plga) nanoparticles","volume":"29","author":"Chung","year":"2008","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1021\/am406008k","article-title":"Construction and evaluation of fe(3)o(4)-based plga nanoparticles carrying rtpa used in the detection of thrombosis and in targeted thrombolysis","volume":"6","author":"Zhou","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.biomaterials.2017.11.047","article-title":"Thrombolytic therapy based on fucoidan-functionalized polymer nanoparticles targeting P-selectin","volume":"156","author":"Juenet","year":"2018","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1002\/adma.201502243","article-title":"Multifunctional Thrombin-Activatable Polymer Capsules for Specific Targeting to Activated Platelets","volume":"27","author":"Gunawan","year":"2015","journal-title":"Adv. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7826","DOI":"10.1021\/acsnano.8b01977","article-title":"Targeted Treatment of Ischemic and Fibrotic Complications of Myocardial Infarction Using a Dual-Delivery Microgel Therapeutic","volume":"12","author":"Mihalko","year":"2018","journal-title":"ACS Nano"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2011.12.032","article-title":"Functionalized carriers for the improved delivery of plasminogen activators","volume":"424","author":"Vaidya","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, H.-A., Ma, Y.-H., Hsu, T.-Y., and Chen, J.-P. (2020). Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082690"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jconrel.2010.07.127","article-title":"An ultrasound-responsive nano delivery system of tissue-type plasminogen activator for thrombolytic therapy","volume":"147","author":"Uesugi","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1016\/j.jacc.2012.08.1008","article-title":"A New Drug Delivery System for Intravenous Coronary Thrombolysis with Thrombus Targeting and Stealth Activity Recoverable by Ultrasound","volume":"60","author":"Kawata","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1700379","DOI":"10.1002\/mabi.201700379","article-title":"Erythrocyte-Derived Nanoparticles as a Theranostic Agent for Near-Infrared Fluorescence Imaging and Thrombolysis of Blood Clots","volume":"18","author":"Vankayala","year":"2018","journal-title":"Macromol. Biosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1021\/acsnano.9b01798","article-title":"Sequentially Site-Specific Delivery of Thrombolytics and Neuroprotectant for Enhanced Treatment of Ischemic Stroke","volume":"13","author":"Xu","year":"2019","journal-title":"ACS Nano"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1021\/acsnano.7b06560","article-title":"Molecularly Engineered Theranostic Nanoparticles for Thrombosed Vessels: H2O2-Activatable Contrast-Enhanced Photoacoustic Imaging and Antithrombotic Therapy","volume":"12","author":"Jung","year":"2018","journal-title":"ACS Nano"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1021\/acsnano.7b02308","article-title":"Fibrin-Targeted and H2O2-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels","volume":"11","author":"Kang","year":"2017","journal-title":"ACS Nano"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.nano.2017.12.019","article-title":"The diosgenin prodrug nanoparticles with ph-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk","volume":"14","author":"Wei","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.biomaterials.2017.03.012","article-title":"Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis","volume":"128","author":"Pawlowski","year":"2017","journal-title":"Biomaterals"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1080\/10837450.2019.1621899","article-title":"MMP-2-responsive gelatin nanoparticles for synergistic tumor therapy","volume":"24","author":"Xu","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"977","DOI":"10.2217\/nnm-2016-0419","article-title":"Gelatin-albumin hybrid nanoparticles as matrix metalloproteinases-degradable delivery systems for breast cancer therapy","volume":"12","author":"Shargh","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1126\/science.1217815","article-title":"Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels","volume":"337","author":"Korin","year":"2012","journal-title":"Science"},{"key":"ref_58","first-page":"7","article-title":"Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications","volume":"7","author":"Croissant","year":"2018","journal-title":"Adv. Heal. Mater."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1901378","DOI":"10.1002\/advs.201901378","article-title":"Metal-organic-framework-derived carbon nanostructures for site-specific dual-modality photothermal\/photodynamic thrombus therapy","volume":"6","author":"Zhang","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101992","DOI":"10.1016\/j.nano.2019.03.014","article-title":"Thrombolysis induced by intravenous administration of plasminogen activator in magnetoliposomes: Dual targeting by magnetic and thermal manipulation","volume":"20","author":"Liu","year":"2019","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1039\/C5TB02579F","article-title":"Magnetically controlled release of recombinant tissue plasminogen activator from chitosan nanocomposites for targeted thrombolysis","volume":"4","author":"Chen","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12939","DOI":"10.1021\/am504270c","article-title":"Synthesis of Multifunctional Magnetic NanoFlakes for Magnetic Resonance Imaging, Hyperthermia, and Targeting","volume":"6","author":"Cervadoro","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"32988","DOI":"10.1021\/acsami.8b09423","article-title":"Tissue Plasminogen Activator-Porous Magnetic Microrods for Targeted Thrombolytic Therapy after Ischemic Stroke","volume":"10","author":"Hu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.thromres.2011.11.010","article-title":"Thrombolytic efficacy of tissue plasminogen activator-loaded echogenic liposomes in a rabbit thrombus model","volume":"130","author":"Laing","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jconrel.2019.07.017","article-title":"In vivo ultrasound-activated delivery of recombinant tissue plasminogen activator from the cavity of sub-micrometric capsules","volume":"308","author":"Poupard","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.neuropharm.2007.12.007","article-title":"Neuroprotection for ischemic stroke: Past, present and future","volume":"55","author":"Ginsberg","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_67","first-page":"2854","article-title":"Recent advances in the development of nanomedicines for the treatment of ischemic stroke","volume":"6","author":"Tian","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.ejphar.2018.06.028","article-title":"Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches","volume":"833","author":"Shekhar","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3389\/fphar.2019.00630","article-title":"Immunomodulatory Therapeutic Strategies in Stroke","volume":"10","author":"Malone","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"98","DOI":"10.2174\/1570161113666150923111329","article-title":"Anti-inflammatory strategies in stroke: A potential therapeutic target","volume":"14","author":"Siniscalchi","year":"2015","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.biomaterials.2017.10.012","article-title":"Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy","volume":"150","author":"Tian","year":"2018","journal-title":"Biomaterals"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1021\/acsnano.0c07973","article-title":"Neutrophil-like Cell-Membrane-Coated Nanozyme Therapy for Ischemic Brain Damage and Long-Term Neurological Functional Recovery","volume":"15","author":"Feng","year":"2021","journal-title":"ACS Nano"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.ijpharm.2017.10.032","article-title":"PLGA-PEG nanoparticles for targeted delivery of the mTOR\/PI3kinase inhibitor dactolisib to inflamed endothelium","volume":"548","author":"Gholizadeh","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.apsb.2017.12.002","article-title":"Biomimetic nanoparticles for inflammation targeting","volume":"8","author":"Jin","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1477-3155-10-25","article-title":"Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent","volume":"10","author":"Paulis","year":"2012","journal-title":"J. Nanobiotechnol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3346\/jkms.1999.14.3.245","article-title":"Time-dependent expression of icam-1 & vcam-1 on coronaries of the heterotopically transplanted mouse heart","volume":"14","author":"Lee","year":"1999","journal-title":"J. Korean Med Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/btm2.10050","article-title":"ICAM-1-targeted nanocarriers attenuate endothelial release of soluble ICAM-1, an inflammatory regulator","volume":"2","author":"Manthe","year":"2017","journal-title":"Bioeng. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/smll.200901158","article-title":"Effect of surface properties on nanoparticle-cell interactions","volume":"6","author":"Verma","year":"2010","journal-title":"Small"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/mt.2008.127","article-title":"Control of Endothelial Targeting and Intracellular Delivery of Therapeutic Enzymes by Modulating the Size and Shape of ICAM-1-targeted Carriers","volume":"16","author":"Muro","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/nano.2006.1.1.51","article-title":"Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery","volume":"1","author":"Shenoy","year":"2006","journal-title":"Int. J. Nanomed."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jconrel.2019.07.026","article-title":"Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions","volume":"309","author":"Brown","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/5194780","article-title":"Physical Properties of Nanoparticles That Result in Improved Cancer Targeting","volume":"2020","author":"Zein","year":"2020","journal-title":"J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ahmadinejad, F., M\u00f8ller, S.G., Hashemzadeh-Chaleshtori, M., Bidkhori, G., and Jami, M.-S. (2017). Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress. Antioxidants, 6.","DOI":"10.3390\/antiox6030051"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1021\/acsbiomaterials.0c01197","article-title":"Ischemia Reperfusion Injury: Opportunities for Nanoparticles","volume":"6","author":"Zang","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"107494","DOI":"10.1016\/j.intimp.2021.107494","article-title":"Nanoparticles of resveratrol attenuates oxidative stress and inflammation after ischemic stroke in rats","volume":"94","author":"Ashafaq","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_86","first-page":"480","article-title":"Neuroprotective potential of cerium oxide nanoparticles for focal cerebral ischemic stroke","volume":"36","author":"Zhou","year":"2016","journal-title":"Acta Acad. Med. Wuhan"},{"key":"ref_87","first-page":"292","article-title":"A novel mechanism of neuroprotection: Blood glutamate grabber","volume":"36","author":"Castillo","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1021\/acs.nanolett.6b01988","article-title":"Nanostructured Antagonist of Extrasynaptic NMDA Receptors","volume":"16","author":"Savchenko","year":"2016","journal-title":"Nano Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S1474-4422(18)30323-5","article-title":"The role of plasminogen activators in stroke treatment: Fibrinolysis and beyond","volume":"17","author":"Thiebaut","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1096\/fj.201601209R","article-title":"Combination therapy with liposomal neuroprotectants and tissue plasminogen activator for treatment of ischemic stroke","volume":"31","author":"Fukuta","year":"2017","journal-title":"FASEB J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"119209","DOI":"10.1016\/j.biomaterials.2019.05.020","article-title":"Encapsulation of tissue plasminogen activator in ph-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment\u2014Synergistic effect of thrombolysis and antioxidant","volume":"215","author":"Mei","year":"2019","journal-title":"Biomaterials"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"908","DOI":"10.3389\/fneur.2019.00908","article-title":"Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment","volume":"10","author":"Castillo","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.pneurobio.2013.11.007","article-title":"Cell based therapies for ischemic stroke: From basic science to bedside","volume":"115","author":"Liu","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.carbpol.2012.09.098","article-title":"Dextran stabilized iron oxide nanoparticles: Synthesis, characterization and in vitro studies","volume":"92","author":"Easo","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1021\/cr068445e","article-title":"Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications","volume":"108","author":"Laurent","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0022-1759(82)90007-2","article-title":"Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic separation of cells","volume":"52","author":"Molday","year":"1982","journal-title":"J. Immunol. Methods"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"40758","DOI":"10.1038\/srep40758","article-title":"Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia","volume":"7","author":"Argibay","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/cmmi.362","article-title":"MR imaging for the longevity of mesenchymal stem cells labeled with poly-L-lysine-Resovist complexes","volume":"5","author":"Liu","year":"2010","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.biomaterials.2010.08.075","article-title":"Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling","volume":"32","author":"Soenen","year":"2011","journal-title":"Biomaterals"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1021\/mp0500014","article-title":"Iron Oxide Nanoparticles for Sustained Delivery of Anticancer Agents","volume":"2","author":"Jain","year":"2005","journal-title":"Mol. Pharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1163\/156856208786440451","article-title":"Pluronic\/chitosan shell cross-linked nanocapsules encapsulating magnetic nanoparticles","volume":"19","author":"Bae","year":"2008","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11839","DOI":"10.1073\/pnas.0404474101","article-title":"Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex","volume":"101","author":"Kelly","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1460-9568.2007.05702.x","article-title":"Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum","volume":"26","author":"Darsalia","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/scd.2008.0253","article-title":"Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect","volume":"18","author":"Fischer","year":"2009","journal-title":"Stem Cells Dev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3389\/fimmu.2012.00297","article-title":"Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion","volume":"3","author":"Eggenhofer","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-22750-7","article-title":"Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking","volume":"8","author":"Ezquer","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1161\/STROKEAHA.115.009854","article-title":"Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke","volume":"46","author":"Acosta","year":"2015","journal-title":"Stroke"},{"key":"ref_108","first-page":"653","article-title":"Effects of Administration Route on Migration and Distribution of Neural Progenitor Cells Transplanted into Rats with Focal Cerebral Ischemia, an MRI Study","volume":"30","author":"Li","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.scr.2012.02.002","article-title":"Intravenous and intra-arterial administration of bone marrow mononuclear cells after focal cerebral ischemia: Is there a difference in biodistribution and efficacy?","volume":"9","author":"Silva","year":"2012","journal-title":"Stem Cell Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1161\/STROKEAHA.111.000821","article-title":"Intra-Arterial Delivery Is Not Superior to Intravenous Delivery of Autologous Bone Marrow Mononuclear Cells in Acute Ischemic Stroke","volume":"44","author":"Yang","year":"2013","journal-title":"Stroke"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.nano.2013.06.005","article-title":"In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies","volume":"10","author":"Carenza","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/5\/757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:04:23Z","timestamp":1760162663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/5\/757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":111,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["pharmaceutics13050757"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13050757","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]}}}