Targeted nano-delivery strategies for facilitating thrombolysis treatment in ischemic stroke

References

• Absar S, Choi S, Ahsan F, et al. (2013). Preparation and characterization of anionic oligopeptide-modified tissue plasminogen activator for triggered delivery: an approach for localized thrombolysis. Thromb Res 131:e91–e99.
   PubMed Web of Science ®Google Scholar
• Absar S, Choi S, Yang VC, Kwon YM. (2012). Heparin-triggered release of camouflaged tissue plasminogen activator for targeted thrombolysis. J Control Release 157:46–54.
   PubMed Web of Science ®Google Scholar
• Absar S, Kwon YM, Ahsan F. (2014). Bio-responsive delivery of tissue plasminogen activator for localized thrombolysis. J Control Release 177:42–50.
   PubMed Web of Science ®Google Scholar
• Abu Fanne R, Nassar T, Yarovoi S, et al. (2010). Blood-brain barrier permeability and tPA-mediated neurotoxicity. Neuropharmacology 58:972–80.
   PubMed Web of Science ®Google Scholar
• Alexandrov AV, Köhrmann M, Soinne L, et al. (2019). Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurol 18:338–47.
   PubMed Web of Science ®Google Scholar
• Alexandrov AV, Molina CA, Grotta JC, et al. (2004). Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351:2170–8.
   PubMed Web of Science ®Google Scholar
• Alonso A, Dempfle CE, Della Martina A, et al. (2009). In vivo clot lysis of human thrombus with intravenous abciximab immunobubbles and ultrasound. Thromb Res 124:70–4.
   PubMed Web of Science ®Google Scholar
• Bachelet L, Bertholon I, Lavigne D, et al. (2009). Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets. Biochim Biophys Acta 1790:141–6.
   PubMed Web of Science ®Google Scholar
• Benjamin EJ, Virani SS, Callaway CW, et al. (2018). Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 137:e67–e492.
   PubMed Web of Science ®Google Scholar
• Berkhemer OA, Fransen PS, Beumer D, et al. (2015). A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 372:11–20.
   PubMed Web of Science ®Google Scholar
• Chan PH. (2001). Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14.
   PubMed Web of Science ®Google Scholar
• Chen H-A, Ma Y-H, Hsu T-Y, 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. IJMS 21:2690.
   Google Scholar
• Chen J-P, Liu C-H, Hsu H-L, et al. (2016). Magnetically controlled release of recombinant tissue plasminogen activator from chitosan nanocomposites for targeted thrombolysis. J Mater Chem B 4:2578–90.
   PubMed Web of Science ®Google Scholar
• Chen Z, Wang Z, Gu Z. (2019). Bioinspired and biomimetic nanomedicines. Acc Chem Res 52:1255–64.
   PubMed Web of Science ®Google Scholar
• Colasuonno M, Palange AL, Aid R, et al. (2018). Erythrocyte-inspired discoidal polymeric nanoconstructs carrying tissue plasminogen activator for the enhanced lysis of blood clots. ACS Nano 12:12224–37.
   PubMed Web of Science ®Google Scholar
• Colucci M, Paramo JA, Collen D. (1986). Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo. J Lab Clin Med 108:53–9.
   PubMed Web of Science ®Google Scholar
• Correa-Paz C, Navarro Poupard MF, Polo E, et al. (2019). In vivo ultrasound-activated delivery of recombinant tissue plasminogen activator from the cavity of sub-micrometric capsules. J Control Release 308:162–71.
   PubMed Web of Science ®Google Scholar
• Daffertshofer M, Hennerici M. (2003). Ultrasound in the treatment of ischaemic stroke. Lancet Neurol 2:283–90.
   PubMed Web of Science ®Google Scholar
• Danielyan K, Ganguly K, Ding BS, et al. (2008). Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator. Circulation 118:1442–9.
   PubMed Web of Science ®Google Scholar
• De Meyer SF, Andersson T, Baxter B, et al. (2017). Analyses of thrombi in acute ischemic stroke: a consensus statement on current knowledge and future directions. Int J Stroke 12:606–14.
   PubMed Web of Science ®Google Scholar
• De Saint Victor M, Barnsley LC, Carugo D, et al. (2019). Sonothrombolysis with magnetically targeted microbubbles. Ultrasound Med Biol 45:1151–63.
   PubMed Web of Science ®Google Scholar
• De Saint Victor M, Crake C, Coussios CC, Stride E. (2014). Properties, characteristics and applications of microbubbles for sonothrombolysis. Expert Opin Drug Deliv 11:187–209.
   PubMed Web of Science ®Google Scholar
• Dehaini D, Fang RH, Zhang L. (2016). Biomimetic strategies for targeted nanoparticle delivery. Bioeng Transl Med 1:30–46.
   PubMed Web of Science ®Google Scholar
• Deng J, Mei H, Shi W, et al. (2018). Recombinant tissue plasminogen activator-conjugated nanoparticles effectively targets thrombolysis in a rat model of middle cerebral artery occlusion. Curr Med SCI 38:427–35.
   PubMed Web of Science ®Google Scholar
• Dirnagl U, Iadecola C, Moskowitz MA. (1999). Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–7.
   PubMed Web of Science ®Google Scholar
• Eggers J, Koch B, Meyer K, et al. (2003). Effect of ultrasound on thrombolysis of middle cerebral artery occlusion. Ann Neurol 53:797–800.
   PubMed Web of Science ®Google Scholar
• Epshtein M, Korin N. (2017). Shear targeted drug delivery to stenotic blood vessels. J Biomech 50:217–21.
   PubMed Web of Science ®Google Scholar
• Everbach EC, Francis CW. (2000). Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz. Ultrasound Med Biol 26:1153–60.
   PubMed Web of Science ®Google Scholar
• Fang RH, Jiang Y, Fang JC, Zhang L. (2017). Cell membrane-derived nanomaterials for biomedical applications. Biomaterials 128:69–83.
   PubMed Web of Science ®Google Scholar
• Francis CW, Blinc A, Lee S, Cox C. (1995). Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol 21:419–24.
   PubMed Web of Science ®Google Scholar
• Fukuta T, Asai T, Yanagida Y, et al. (2017). Combination therapy with liposomal neuroprotectants and tissue plasminogen activator for treatment of ischemic stroke. Faseb J 31:1879–90.
   PubMed Web of Science ®Google Scholar
• Fukuta T, Yanagida Y, Asai T, Oku N. (2018). Co-administration of liposomal fasudil and tissue plasminogen activator ameliorated ischemic brain damage in occlusion model rats prepared by photochemically induced thrombosis. Biochem Biophys Res Commun 495:873–7.
   PubMed Web of Science ®Google Scholar
• Ginsberg MD. (2008). Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 55:363–89.
   PubMed Web of Science ®Google Scholar
• Global Burden of Diseases 2017 Disease and Injury Incidence and Prevalence Collaborators. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392:1789–858.
   PubMed Web of Science ®Google Scholar
• Hagisawa K, Nishioka T, Suzuki R, et al. (2013). Thrombus-targeted perfluorocarbon-containing liposomal bubbles for enhancement of ultrasonic thrombolysis: in vitro and in vivo study. J Thromb Haemost 11:1565–73.
   PubMed Web of Science ®Google Scholar
• Henderson SJ, Weitz JI, Kim PY. (2018). Fibrinolysis: strategies to enhance the treatment of acute ischemic stroke. J Thromb Haemost 16:1932–40.
   PubMed Web of Science ®Google Scholar
• Heo JH, Lee KY, Kim SH, Kim DI. (2003). Immediate reocclusion following a successful thrombolysis in acute stroke: a pilot study. Neurology 60:1684–7.
   PubMed Web of Science ®Google Scholar
• Hu CM, Fang RH, Wang KC, et al. (2015). Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526:118–21.
   PubMed Web of Science ®Google Scholar
• Hu J, Huang S, Zhu L, et al. (2018). Tissue plasminogen activator-porous magnetic microrods for targeted thrombolytic therapy after ischemic stroke. ACS Appl Mater Interfaces 10:32988–97.
   PubMed Web of Science ®Google Scholar
• Hua X, Liu P, Gao YH, et al. (2010). Construction of thrombus-targeted microbubbles carrying tissue plasminogen activator and their in vitro thrombolysis efficacy: a primary research. J Thromb Thrombolysis 30:29–35.
   PubMed Web of Science ®Google Scholar
• Hua X, Zhou L, Liu P, et al. (2014). In vivo thrombolysis with targeted microbubbles loading tissue plasminogen activator in a rabbit femoral artery thrombus model. J Thromb Thrombolysis 38:57–64.
   PubMed Web of Science ®Google Scholar
• Huang G, Zhou Z, Srinivasan R, et al. (2008). Affinity manipulation of surface-conjugated RGD peptide to modulate binding of liposomes to activated platelets. Biomaterials 29:1676–85.
   PubMed Web of Science ®Google Scholar
• Huang L, Wang J, Huang S, et al. (2019). Polyacrylic acid-coated nanoparticles loaded with recombinant tissue plasminogen activator for the treatment of mice with ischemic stroke. Biochem Biophys Res Commun 516:565–70.
   PubMed Web of Science ®Google Scholar
• Ishiguro M, Kawasaki K, Suzuki Y, et al. (2012). A Rho kinase (ROCK) inhibitor, fasudil, prevents matrix metalloproteinase-9-related hemorrhagic transformation in mice treated with tissue plasminogen activator. Neuroscience 220:302–12.
   PubMed Web of Science ®Google Scholar
• Juenet M, Aid-Launais R, Li B, et al. (2018). Thrombolytic therapy based on fucoidan-functionalized polymer nanoparticles targeting P-selectin. Biomaterials 156:204–16.
   PubMed Web of Science ®Google Scholar
• Kandadai MA, Mukherjee P, Shekhar H, et al. (2016). Microfluidic manufacture of rt-PA -loaded echogenic liposomes. Biomed Microdevices 18:48.
   PubMed Web of Science ®Google Scholar
• Kelly MA, Shuaib A, Todd KG. (2006). Matrix metalloproteinase activation and blood-brain barrier breakdown following thrombolysis. Exp Neurol 200:38–49.
   PubMed Web of Science ®Google Scholar
• Kontos HA. (2001). Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke 32:2712–6.
   PubMed Web of Science ®Google Scholar
• Korin N, Gounis MJ, Wakhloo AK, Ingber DE. (2015). Targeted drug delivery to flow-obstructed blood vessels using mechanically activated nanotherapeutics. JAMA Neurol 72:119–22.
   PubMed Web of Science ®Google Scholar
• Korin N, Kanapathipillai M, Matthews BD, et al. (2012). Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 337:738–42.
   PubMed Web of Science ®Google Scholar
• Kvistad CE, Nacu A, Novotny V, et al. (2018). Contrast-enhanced sonothrombolysis in acute ischemic stroke patients without intracranial large-vessel occlusion. Acta Neurol Scand 137:256–61.
   PubMed Web of Science ®Google Scholar
• Laing ST, Moody MR, Kim H, et al. (2012). Thrombolytic efficacy of tissue plasminogen activator-loaded echogenic liposomes in a rabbit thrombus model. Thromb Res 130:629–35.
   PubMed Web of Science ®Google Scholar
• Lapchak PA, Araujo DM. (2007). Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opin Emerg Drugs 12:97–112.
   PubMed Web of Science ®Google Scholar
• Lee HJ, Park J, Yoon OJ, et al. (2011). Amine-modified single-walled carbon nanotubes protect neurons from injury in a rat stroke model. Nat Nanotechnol 6:121–5.
   PubMed Web of Science ®Google Scholar
• Li M, Liu Y, Chen J, et al. (2018). Platelet bio-nanobubbles as microvascular recanalization nanoformulation for acute ischemic stroke lesion theranostics. Theranostics 8:4870–83.
   PubMed Web of Science ®Google Scholar
• Liu CH, Hsu HL, Chen JP, et al. (2019). Thrombolysis induced by intravenous administration of plasminogen activator in magnetoliposomes: dual targeting by magnetic and thermal manipulation. Nanomedicine 20:101992
   PubMed Web of Science ®Google Scholar
• Ma YH, Wu SY, Wu T, et al. (2009). Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles. Biomaterials 30:3343–51.
   PubMed Web of Science ®Google Scholar
• Maeda H, Nakamura H, Fang J. (2013). The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65:71–9.
   PubMed Web of Science ®Google Scholar
• Marosfoi MG, Korin N, Gounis MJ, et al. (2015). Shear-activated nanoparticle aggregates combined with temporary endovascular bypass to treat large vessel occlusion. Stroke 46:3507–13.
   PubMed Web of Science ®Google Scholar
• Marsh JN, Hu G, Scott MJ, et al. (2011). A fibrin-specific thrombolytic nanomedicine approach to acute ischemic stroke. Nanomedicine (Lond) 6:605–15.
   PubMed Web of Science ®Google Scholar
• Marshall RS. (2015). Progress in intravenous thrombolytic therapy for acute stroke. JAMA Neurol 72:928–34.
   PubMed Web of Science ®Google Scholar
• Mei T, Kim A, Vong LB, et al. (2019). Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment - synergistic effect of thrombolysis and antioxidant. Biomaterials 215:119209
   PubMed Web of Science ®Google Scholar
• Miller DL. (1987). A review of the ultrasonic bioeffects of microsonation, gas-body activation, and related cavitation-like phenomena. Ultrasound Med Biol 13:443–70.
   PubMed Web of Science ®Google Scholar
• Miller DL. (1988). Particle gathering and microstreaming near ultrasonically activated gas-filled micropores. J Acoust Soc Am 84:1378–87.
   PubMed Web of Science ®Google Scholar
• Murciano JC, Higazi AA, Cines DB, Muzykantov VR. (2009). Soluble urokinase receptor conjugated to carrier red blood cells binds latent pro-urokinase and alters its functional profile. J Control Release 139:190–6.
   PubMed Web of Science ®Google Scholar
• Murciano JC, Medinilla S, Eslin D, et al. (2003). Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nat Biotechnol 21:891–6.
   PubMed Web of Science ®Google Scholar
• Nacu A, Kvistad CE, Logallo N, et al. (2015). A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS). BMC Neurol 15:110
   PubMed Web of Science ®Google Scholar
• Nacu A, Kvistad CE, Naess H, et al. (2017). NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): randomized controlled contrast-enhanced sonothrombolysis in an unselected acute ischemic stroke population. Stroke 48:335–41.
   PubMed Web of Science ®Google Scholar
• Pawlowski CL, Li W, Sun M, et al. (2017). Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis. Biomaterials 128:94–108.
   PubMed Web of Science ®Google Scholar
• Perren F, Loulidi J, Poglia D, et al. (2008). Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis in acute stroke. J Thromb Thrombolysis 25:219–23.
   PubMed Web of Science ®Google Scholar
• Petro M, Jaffer H, Yang J, et al. (2016). Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain. Biomaterials 81:169–80.
   PubMed Web of Science ®Google Scholar
• Polak JF. (2004). Ultrasound energy and the dissolution of thrombus. N Engl J Med 351:2154–5.
   PubMed Web of Science ®Google Scholar
• Powers WJ, Rabinstein AA, Ackerson T, et al. (2018). 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49:e46–e110.
   PubMed Web of Science ®Google Scholar
• Ricci S, Dinia L, Del Sette M, et al. (2012). Sonothrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 6:CD008348.
   Google Scholar
• Rubiera M, Alexandrov AV. (2010). Sonothrombolysis in the management of acute ischemic stroke. Am J Cardiovasc Drugs 10:5–10.
   PubMed Web of Science ®Google Scholar
• Ruggeri ZM. (2002). Platelets in atherothrombosis. Nat Med 8:1227–34.
   PubMed Web of Science ®Google Scholar
• Sakharov DV, Hekkenberg RT, Rijken DC. (2000). Acceleration of fibrinolysis by high-frequency ultrasound: the contribution of acoustic streaming and temperature rise. Thromb Res 100:333–40.
   PubMed Web of Science ®Google Scholar
• Saqqur M, Tsivgoulis G, Nicoli F, et al. (2014). The role of sonolysis and sonothrombolysis in acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials and case-control studies. J Neuroimaging 24:209–20.
   PubMed Web of Science ®Google Scholar
• Saver JL, Goyal M, Bonafe A, et al. (2015). Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 372:2285–95.
   PubMed Web of Science ®Google Scholar
• Saxer T, Zumbuehl A, Müller B. (2013). The use of shear stress for targeted drug delivery. Cardiovasc Res 99:328–33.
   PubMed Web of Science ®Google Scholar
• Schwarz M, Meade G, Stoll P, et al. (2006). Conformation-specific blockade of the integrin GPIIb/IIIa: a novel antiplatelet strategy that selectively targets activated platelets. Circ Res 99:25–33.
   PubMed Web of Science ®Google Scholar
• Seo J, Al-Hilal TA, Jee JG, et al. (2018). A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots. Nanomedicine 14:633–42.
   PubMed Web of Science ®Google Scholar
• Shaw GJ, Meunier JM, Huang SL, et al. (2009). Ultrasound-enhanced thrombolysis with tPA-loaded echogenic liposomes. Thromb Res 124:306–10.
   PubMed Web of Science ®Google Scholar
• Shekhar H, Bader KB, Huang S, et al. (2017). In vitro thrombolytic efficacy of echogenic liposomes loaded with tissue plasminogen activator and octafluoropropane gas. Phys Med Biol 62:517–38.
   PubMed Web of Science ®Google Scholar
• Singh P, Kaur R, Kaur A. (2013). Clot composition and treatment approach to acute ischemic stroke: the road so far. Ann Indian Acad Neurol 16:494–7.
   PubMed Web of Science ®Google Scholar
• Smith DA, Vaidya SS, Kopechek JA, et al. (2010). Ultrasound-triggered release of recombinant tissue-type plasminogen activator from echogenic liposomes. Ultrasound Med Biol 36:145–57.
   PubMed Web of Science ®Google Scholar
• Tadayon A, Jamshidi R, Esmaeili A. (2016). Targeted thrombolysis of tissue plasminogen activator and streptokinase with extracellular biosynthesis nanoparticles using optimized Streptococcus equi supernatant. Int J Pharm 501:300–10.
   PubMedGoogle Scholar
• Takamiya M, Miyamoto Y, Yamashita T, et al. (2012). Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice. Neuroscience 221:47–55.
   PubMed Web of Science ®Google Scholar
• Teng Y, Jin H, Nan D, et al. (2018). In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model. Bioact Mater 3:102–9.
   PubMed Web of Science ®Google Scholar
• Tiebosch IA, Crielaard BJ, Bouts MJ, et al. (2012). Combined treatment with recombinant tissue plasminogen activator and dexamethasone phosphate-containing liposomes improves neurological outcome and restricts lesion progression after embolic stroke in rats. J Neurochem 123(Suppl 2):65–74.
   PubMedGoogle Scholar
• Tiukinhoy-Laing SD, Buchanan K, Parikh D, et al. (2007). Fibrin targeting of tissue plasminogen activator-loaded echogenic liposomes. J Drug Target 15:109–14.
   PubMed Web of Science ®Google Scholar
• Tsivgoulis G, Eggers J, Ribo M, et al. (2010). Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke 41:280–7.
   PubMed Web of Science ®Google Scholar
• Uesugi Y, Kawata H, Jo J, et al. (2010). An ultrasound-responsive nano delivery system of tissue-type plasminogen activator for thrombolytic therapy. J Control Release 147:269–77.
   PubMed Web of Science ®Google Scholar
• Vankayala R, Corber SR, Mac JT, et al. (2018). Erythrocyte-derived nanoparticles as a theranostic agent for near-infrared fluorescence imaging and thrombolysis of blood clots. Macromol Biosci 18:e1700379.
   PubMed Web of Science ®Google Scholar
• Villa CH, Anselmo AC, Mitragotri S, Muzykantov V. (2016). Red blood cells: supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems. Adv Drug Deliv Rev 106:88–103.
   PubMed Web of Science ®Google Scholar
• Villa CH, Pan DC, Zaitsev S, et al. (2015). Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier. Ther Deliv 6:795–826.
   PubMed Web of Science ®Google Scholar
• Wang S, Guo X, Xiu W, et al. (2020). Accelerating thrombolysis using a precision and clot-penetrating drug delivery strategy by nanoparticle-shelled microbubbles. Sci Adv 6:eaaz8204.
   PubMed Web of Science ®Google Scholar
• Wang X, Gkanatsas Y, Palasubramaniam J, et al. (2016). Thrombus-targeted theranostic microbubbles: a new technology towards concurrent rapid ultrasound diagnosis and bleeding-free fibrinolytic treatment of thrombosis. Theranostics 6:726–38.
   PubMed Web of Science ®Google Scholar
• Wang X, Hagemeyer CE, Hohmann JD, et al. (2012). Novel single-chain antibody-targeted microbubbles for molecular ultrasound imaging of thrombosis: validation of a unique noninvasive method for rapid and sensitive detection of thrombi and monitoring of success or failure of thrombolysis in mice. Circulation 125:3117–26.
   PubMed Web of Science ®Google Scholar
• Xu J, Wang X, Yin H, et al. (2019). Sequentially site-specific delivery of thrombolytics and neuroprotectant for enhanced treatment of ischemic stroke. ACS Nano 13:8577–88.
   PubMed Web of Science ®Google Scholar
• Xu J, Zhang Y, Xu J, et al. (2020). Engineered nanoplatelets for targeted delivery of plasminogen activators to reverse thrombus in multiple mouse thrombosis models. Adv Mater 32:e1905145
   PubMed Web of Science ®Google Scholar
• Yaghi S, Willey JZ, Cucchiara B, et al. (2017). Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 48:e343–e61.
   PubMed Web of Science ®Google Scholar
• Yan WC, Chua QW, Ong XJ, et al. (2017). Fabrication of ultrasound-responsive microbubbles via coaxial electrohydrodynamic atomization for triggered release of tPA. J Colloid Interface Sci 501:282–93.
   PubMed Web of Science ®Google Scholar
• Yang HW, Hua MY, Lin KJ, et al. (2012). Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis. Int J Nanomedicine 7:5159–73.
   PubMed Web of Science ®Google Scholar
• Yepes M, Roussel BD, Ali C, Vivien D. (2009). Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic. Trends Neurosci 32:48–55.
   PubMed Web of Science ®Google Scholar
• Zaitsev S, Spitzer D, Murciano JC, et al. (2010a). Targeting of a mutant plasminogen activator to circulating red blood cells for prophylactic fibrinolysis. J Pharmacol Exp Ther 332:1022–31.
   PubMed Web of Science ®Google Scholar
• Zaitsev S, Spitzer D, Murciano JC, et al. (2010b). Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation. Blood 115:5241–8.
   PubMed Web of Science ®Google Scholar
• Zhang B, Kim H, Wu H, et al. (2019). Sonothrombolysis with magnetic microbubbles under a rotational magnetic field. Ultrasonics 98:62–71.
   PubMed Web of Science ®Google Scholar
• Zhou J, Guo D, Zhang Y, et al. (2014). Construction and evaluation of Fe3O4-based PLGA nanoparticles carrying rtPA used in the detection of thrombosis and in targeted thrombolysis. ACS Appl Mater Interfaces 6:5566–76.
   PubMed Web of Science ®Google Scholar