77
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Advances in Engineered Nanoparticles for the Treatment of Ischemic Stroke by Enhancing Angiogenesis

, , , , , , , , , & show all
Pages 4377-4409 | Received 07 Feb 2024, Accepted 02 May 2024, Published online: 17 May 2024

References

  • Virani SS, Alonso A, Benjamin EJ, et al. American heart association council on, C. prevention statistics, S. stroke statistics, heart disease and stroke statistics-2020 update: a report from the American heart association. Circulation. 2020;141(9):e139–e596. doi:10.1161/CIR.0000000000000757
  • Hankey GJ. Stroke. Lancet. 2017;389(10069):641–654. doi:10.1016/S0140-6736(16)30962-X
  • Campbell BCV, De silva DA, Macleod MR, et al. Ischaemic stroke. Nat Rev Dis Primers. 2019;5(1):70. doi:10.1038/s41572-019-0118-8
  • Powers WJ, Rabinstein AA, Ackerson T, et al. 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. Stroke. 2019;50(12):e344–e418. doi:10.1161/STR.0000000000000211
  • Betts KA, Hurley D, Song J, et al. Real-world outcomes of acute ischemic stroke treatment with intravenous recombinant tissue plasminogen activator. J Stroke Cerebrovasc Dis. 2017;26(9):1996–2003. doi:10.1016/j.jstrokecerebrovasdis.2017.06.010
  • Jin H, Bi R, Hu J, et al. Elevated serum lactate dehydrogenase predicts unfavorable outcomes After rt-PA thrombolysis in ischemic stroke patients. Front Neurol. 2022;13:816216. doi:10.3389/fneur.2022.816216
  • Liao J, Li Y, Luo Y, et al. Recent advances in targeted nanotherapies for ischemic stroke. Mol Pharm. 2022;19(9):3026–3041. doi:10.1021/acs.molpharmaceut.2c00383
  • Yang H, Luo Y, Hu H, et al. pH-Sensitive, cerebral vasculature-targeting hydroxyethyl starch functionalized nanoparticles for improved angiogenesis and neurological function recovery in ischemic stroke. Adv Healthc Mater. 2021;10(12):e2100028. doi:10.1002/adhm.202100028
  • Kaushal V, Schlichter LC. Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra. J Neurosci. 2008;28(9):2221–2230. doi:10.1523/JNEUROSCI.5643-07.2008
  • Lo EH. A new penumbra: transitioning from injury into repair after stroke. Nat Med. 2008;14(5):497–500. doi:10.1038/nm1735
  • Hermann DM, Zechariah A. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. J Cereb Blood Flow Metab. 2009;29(10):1620–1643. doi:10.1038/jcbfm.2009.100
  • Snapyan M, Lemasson MS, Brill M, et al. Saghatelyan, Vasculature guides migrating neuronal precursors in the adult mammalian forebrain via brain-derived neurotrophic factor signaling. J Neurosci. 2009;29(13):4172–4188. doi:10.1523/JNEUROSCI.4956-08.2009
  • Teng H, Zhang ZG, Wang L, et al. Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke. J Cereb Blood Flow Metab. 2008;28(4):764–771. doi:10.1038/sj.jcbfm.9600573
  • Yang Y, Torbey MT. Angiogenesis and blood-brain barrier permeability in vascular remodeling after stroke. Curr Neuropharmacol. 2020;18(12):1250–1265. doi:10.2174/1570159X18666200720173316
  • Xie C, Liao J, Zhang N, et al. Advanced nano drug delivery systems for neuroprotection against ischemic stroke. Chin. Chem. Lett. 2024;35(2):109149. doi:10.1016/j.cclet.2023.109149
  • Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediators Inflamm. 2013;2013:127170. doi:10.1155/2013/127170
  • Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307. doi:10.1038/nature10144
  • Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007;8(6):464–478. doi:10.1038/nrm2183
  • Freedman SB, Isner JM. Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol. 2001;33(3):379–393. doi:10.1006/jmcc.2000.1329
  • Ribatti D, Conconi MT, Nussdorfer GG. Nonclassic endogenous novel [corrected] regulators of angiogenesis. Pharmacol Rev. 2007;59(2):185–205. doi:10.1124/pr.59.2.3
  • Zhao L, Johnson T, Liu D. Therapeutic angiogenesis of adipose-derived stem cells for ischemic diseases. Stem Cell Res Ther. 2017;8(1):125. doi:10.1186/s13287-017-0578-2
  • Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–198. doi:10.1146/annurev-med-040210-162544
  • Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16–20. doi:10.1021/nn900002m
  • Kaviarasi S, Yuba E, Harada A, Krishnan UM. Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia. J Control Release. 2019;300:22–45. doi:10.1016/j.jconrel.2019.02.031
  • Knowland D, Arac A, Sekiguchi KJ, et al. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron. 2014;82(3):603–617. doi:10.1016/j.neuron.2014.03.003
  • Dong X, Gao J, Su Y, Wang Z. Nanomedicine for ischemic stroke. Int J Mol Sci. 2020;21(20):7600. doi:10.3390/ijms21207600
  • Pulicherla KK, Verma MK. Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements. AAPS Pharm Sci Tech. 2015;16(2):223–233. doi:10.1208/s12249-015-0287-z
  • Chik MW, Hussain Z, Zulkefeli M, et al. Polymer-wrapped single-walled carbon nanotubes: a transformation toward better applications in healthcare. Drug Deliv Transl Res. 2019;9(2):578–594. doi:10.1007/s13346-018-0505-9
  • Panagiotou S, Saha S. Therapeutic benefits of nanoparticles in stroke. Front Neurosci. 2015;9:182. doi:10.3389/fnins.2015.00182
  • Sarmah D, Saraf J, Kaur H, et al. Stroke management: an emerging role of nanotechnology. Micromachines. 2017;8(9):1.
  • Kyle S, Saha S. Nanotechnology for the detection and therapy of stroke. Adv Healthc Mater. 2014;3(11):1703–1720. doi:10.1002/adhm.201400009
  • Shen J, Zhao Z, Shang W, et al. Fabrication and evaluation a transferrin receptor targeting nano-drug carrier for cerebral infarction treatment. Artif Cells Nanomed Biotechnol. 2019;47(1):192–200. doi:10.1080/21691401.2018.1548471
  • Carenza E, Jordan O, Martinez-San Segundo P, et al. Encapsulation of VEGF(165) into magnetic PLGA nanocapsules for potential local delivery and bioactivity in human brain endothelial cells. J Mater Chem B. 2015;3(12):2538–2544. doi:10.1039/C4TB01895H
  • Deng L, Zhang F, Wu Y, et al. RGD-modified nanocarrier-mediated targeted delivery of HIF-1alpha-AA Plasmid DNA to cerebrovascular endothelial cells for ischemic stroke treatment. ACS Biomater Sci Eng. 2019;5(11):6254–6264. doi:10.1021/acsbiomaterials.9b01362
  • Wang C, Lin G, Luan Y, et al. HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke. Biomaterials. 2019;197:229–243. doi:10.1016/j.biomaterials.2018.05.053
  • Shen J, Zhao Z, Shang W, et al. Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction. Artif Cells Nanomed Biotechnol. 2018;46(sup2):894–903. doi:10.1080/21691401.2018.1471483
  • Ferreira R, Fonseca MC, Santos T, et al. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia. Nanoscale. 2016;8(15):8126–8137. doi:10.1039/C5NR09077F
  • Petro M, Jaffer H, Yang J, Kabu S, Morris VB, Labhasetwar V. Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain. Biomaterials. 2016;81:169–180. doi:10.1016/j.biomaterials.2015.12.009
  • Lu X, Dong J, Zheng D, Li X, Ding D, Xu H. Reperfusion combined with intraarterial administration of resveratrol-loaded nanoparticles improved cerebral ischemia-reperfusion injury in rats. Nanomedicine. 2020;28:102208. doi:10.1016/j.nano.2020.102208
  • Li X, Han Z, Wang T, et al. Cerium oxide nanoparticles with antioxidative neurorestoration for ischemic stroke. Biomaterials. 2022;291:121904. doi:10.1016/j.biomaterials.2022.121904
  • Wang J, Su Q, Lv Q, et al. Oxygen-generating cyanobacteria powered by upconversion-nanoparticles-converted near-infrared light for ischemic stroke treatment. Nano Lett. 2021;21(11):4654–4665. doi:10.1021/acs.nanolett.1c00719
  • Li Y, Zhang M, Li S, et al. Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury. Asian J Pharm Sci. 2023;18(2):100783. doi:10.1016/j.ajps.2023.100783
  • Xia Y, Ling X, Hu G, et al. Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke. Stem Cell Res Ther. 2020;11(1):313. doi:10.1186/s13287-020-01834-0
  • Gregorius J, Wang C, Stambouli O, et al. Small extracellular vesicles obtained from hypoxic mesenchymal stromal cells have unique characteristics that promote cerebral angiogenesis, brain remodeling and neurological recovery after focal cerebral ischemia in mice. Basic Res Cardiol. 2021;116(1):40. doi:10.1007/s00395-021-00881-9
  • Mohamud Yusuf A, Hagemann N, Zhang X, et al. Acid sphingomyelinase deactivation post-ischemia promotes brain angiogenesis and remodeling by small extracellular vesicles. Basic Res Cardiol. 2022;117(1):43. doi:10.1007/s00395-022-00950-7
  • Zhang L, Wei W, Ai X, et al. Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-beta/Smad2/3 pathway. Cell Death Dis. 2021;12(11):1068. doi:10.1038/s41419-021-04363-7
  • Wang C, Yang X, Jiang Y, et al. Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke. J Nanobiotechnology. 2022;20(1):249. doi:10.1186/s12951-022-01461-2
  • Katas H, Wen CY, Siddique MI, Hussain Z, Mohd Fadhil FH. Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release. Ther Deliv. 2017;8(3):137–150. doi:10.4155/tde-2016-0075
  • Hussain Z, Katas H, Yan SL, Jamaludin D. Efficient colonic delivery of DsiRNA by pectin-coated polyelectrolyte complex nanoparticles: preparation, characterization and improved gastric survivability. Curr Drug Deliv. 2017;14(7):1016–1027. doi:10.2174/1567201814666170224142446
  • Ei Thu H, Hussain Z, Shuid AN. New insight in improving therapeutic efficacy of antipsychotic agents: an overview of improved in vitro and in vivo performance, efficacy upgradation and future prospects. Curr Drug Targets. 2018;19(8):865–876. doi:10.2174/1389450117666161125174625
  • Zia MA, Sohail M, Minhas M, et al. HEMA based pH-sensitive semi IPN microgels for oral delivery; a rationale approach for ketoprofen. Drug Dev Ind Pharm. 2020;46(2):272–282. doi:10.1080/03639045.2020.1716378
  • Chen W, Jiang L, Hu Y, et al. Nanomedicines, an emerging therapeutic regimen for treatment of ischemic cerebral stroke: a review. J Control Release. 2021;340:342–360. doi:10.1016/j.jconrel.2021.10.020
  • Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:238428.
  • Chen C, Mu XY, Zhou Y, et al. Ginsenoside Rg1 enhances the resistance of hematopoietic stem/progenitor cells to radiation-induced aging in mice. Acta Pharmacol Sin. 2014;35(1):143–150. doi:10.1038/aps.2013.136
  • Wang J, Li D, Hou J, Lei H. Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition. Mol Med Rep. 2018;17(2):3186–3193. doi:10.3892/mmr.2017.8221
  • Xie CL, Li JH, Wang WW, Zheng GQ, Wang LX. Neuroprotective effect of ginsenoside-Rg1 on cerebral ischemia/reperfusion injury in rats by downregulating protease-activated receptor-1 expression. Life Sci. 2015;121:145–151. doi:10.1016/j.lfs.2014.12.002
  • Li Y-B, Wang Y, Tang J-P, Chen D, Wang S-L. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy. Neural Regen Res. 2015;10(5):753–759. doi:10.4103/1673-5374.156971
  • Shen HH. Core Concept: circumventing the blood-brain barrier. Proc Natl Acad Sci U S A. 2017;114(43):11261–11263. doi:10.1073/pnas.1716187114
  • Nogueira-Librelotto DR, Codevilla CF, Farooqi A, Rolim CM. Transferrin-conjugated nanocarriers as active-targeted drug delivery platforms for cancer therapy. Curr Pharm Des. 2017;23(3):454–466. doi:10.2174/1381612822666161026162347
  • Han L, Li J, Huang S, et al. Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent. Biomaterials. 2011;32(11):2989–2998. doi:10.1016/j.biomaterials.2011.01.005
  • Zhang L, Wang T, Li Q, et al. Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo. Int J Nanomed. 2016;11:2663–2673. doi:10.2147/IJN.S104593
  • Geng X, Ye H, Feng Z, et al. Synthesis and characterization of cisplatin-loaded, EGFR-targeted biopolymer and in vitro evaluation for targeted delivery. J Biomed Mater Res A. 2012;100(10):2839–2848. doi:10.1002/jbm.a.34207
  • Zhang L, Chang J, Zhao Y, et al. Fabrication of a triptolide-loaded and poly-gamma-glutamic acid-based amphiphilic nanoparticle for the treatment of rheumatoid arthritis. Int J Nanomed. 2018;13:2051–2064. doi:10.2147/IJN.S151233
  • Carenza E, Barcelo V, Morancho A, et al. In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies. Nanomedicine. 2014;10(1):225–234. doi:10.1016/j.nano.2013.06.005
  • Bible E, Qutachi O, Chau DY, Alexander MR, Shakesheff KM, Modo M. Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles. Biomaterials. 2012;33(30):7435–7446. doi:10.1016/j.biomaterials.2012.06.085
  • Formiga FR, Pelacho B, Garbayo E, et al. Sustained release of VEGF through PLGA microparticles improves vasculogenesis and tissue remodeling in an acute myocardial ischemia-reperfusion model. J Control Release. 2010;147(1):30–37. doi:10.1016/j.jconrel.2010.07.097
  • Golub JS, Kim YT, Duvall CL, et al. Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth. Am J Physiol Heart Circ Physiol. 2010;298(6):H1959–65. doi:10.1152/ajpheart.00199.2009
  • Rhim T, Lee DY, Lee M. Drug delivery systems for the treatment of ischemic stroke. Pharm Res. 2013;30(10):2429–2444. doi:10.1007/s11095-012-0959-2
  • Des Rieux A, Ucakar BP, Mupendwa B, et al. 3D systems delivering VEGF to promote angiogenesis for tissue engineering. J Control Release. 2011;150(3):272–278. doi:10.1016/j.jconrel.2010.11.028
  • Borselli C, Ungaro F, Oliviero O, et al. Bioactivation of collagen matrices through sustained VEGF release from PLGA microspheres. J Biomed Mater Res A. 2010;92(1):94–102. doi:10.1002/jbm.a.32332
  • Kim J, Cao L, Shvartsman D, Silva EA, Mooney DJ. Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic angiogenesis. Nano Lett. 2011;11(2):694–700. doi:10.1021/nl103812a
  • Liu X, Kaminski MD, Chen H, Torno M, Taylor L, Rosengart AJ. Synthesis and characterization of highly-magnetic biodegradable poly(d,l-lactide-co-glycolide) nanospheres. J Control Release. 2007;119(1):52–58. doi:10.1016/j.jconrel.2006.11.031
  • Okassa LN, Marchais H, Douziech-Eyrolles L, et al. Optimization of iron oxide nanoparticles encapsulation within poly(d,l-lactide-co-glycolide) sub-micron particles. Eur J Pharm Biopharm. 2007;67(1):31–38. doi:10.1016/j.ejpb.2006.12.020
  • Khan M, Dhammu TS, Matsuda F, et al. Promoting endothelial function by S-nitrosoglutathione through the HIF-1alpha/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats. Drug Des Devel Ther. 2015;9:2233–2247. doi:10.2147/DDDT.S77115
  • Doeppner TR, Mlynarczuk-Bialy I, Kuckelkorn U, et al. The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia through HIF1A accumulation and enhanced angioneurogenesis. Brain. 2012;135(Pt 11):3282–3297. doi:10.1093/brain/aws269
  • Zhong Q, Zhou Y, Ye W, Cai T, Zhang X, Deng DY. Hypoxia-inducible factor 1-alpha-AA-modified bone marrow stem cells protect PC12 cells from hypoxia-induced apoptosis, partially through VEGF/PI3K/Akt/FoxO1 pathway. Stem Cells Dev. 2012;21(14):2703–2717. doi:10.1089/scd.2011.0604
  • Bharadwaj VN, Nguyen DT, Kodibagkar VD, Stabenfeldt SE. Nanoparticle-based therapeutics for brain injury. Adv Healthc Mater. 2018;7(1). doi:10.1002/adhm.201700668
  • Berra E, Benizri E, Ginouves A, et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J. 2003;22(16):4082–4090. doi:10.1093/emboj/cdg392
  • Wu S, Nishiyama N, Kano MR, et al. Enhancement of angiogenesis through stabilization of hypoxia-inducible factor-1 by silencing prolyl hydroxylase domain-2 gene. Mol Ther. 2008;16(7):1227–1234. doi:10.1038/mt.2008.90
  • Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292(5516):468–472. doi:10.1126/science.1059796
  • Oh YK, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 2009;61(10):850–862. doi:10.1016/j.addr.2009.04.018
  • Hong CA, Nam YS. Functional nanostructures for effective delivery of small interfering RNA therapeutics. Theranostics. 2014;4(12):1211–1232. doi:10.7150/thno.8491
  • Lin G, Zhu W, Yang L, et al. Delivery of siRNA by MRI-visible nanovehicles to overcome drug resistance in MCF-7/ADR human breast cancer cells. Biomaterials. 2014;35(35):9495–9507. doi:10.1016/j.biomaterials.2014.07.049
  • Liu G, Xie J, Zhang F, et al. N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery. Small. 2011;7(19):2742–2749. doi:10.1002/smll.201100825
  • Yan B, Yao J, Liu JY, et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res. 2015;116(7):1143–1156. doi:10.1161/CIRCRESAHA.116.305510
  • Yan H, Yuan J, Gao L, et al. Long noncoding RNA MEG3 activation of p53 mediates ischemic neuronal death in stroke. Neuroscience. 2016;337:191–199. doi:10.1016/j.neuroscience.2016.09.017
  • Zhou Y, Cheunsuchon P, Nakayama Y, et al. Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene. Development. 2010;137(16):2643–2652. doi:10.1242/dev.045724
  • Gordon FE, Nutt CL, Cheunsuchon P, et al. Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology. 2010;151(6):2443–2452. doi:10.1210/en.2009-1151
  • Su W, Xie W, Shang Q, Su B. The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis. Biomed Res Int. 2015;2015:356893. doi:10.1155/2015/356893
  • He Y, Luo Y, Liang B, Ye L, Lu G, He W. Potential applications of MEG3 in cancer diagnosis and prognosis. Oncotarget. 2017;8(42):73282–73295. doi:10.18632/oncotarget.19931
  • Hui F, Nguyen CTO, He Z, et al. Retinal and cortical blood flow dynamics following systemic blood-neural barrier disruption. Front Neurosci. 2017;11:568. doi:10.3389/fnins.2017.00568
  • Liu Z, Zhang L, He Q, et al. Effect of Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody on regulating the levels of baicalin and amino acids during cerebral ischemia-reperfusion in rats. Int J Pharm. 2015;489(1–2):131–138. doi:10.1016/j.ijpharm.2015.04.049
  • Peng SF, Tseng MT, Ho YC, Wei MC, Liao ZX, Sung HW. Mechanisms of cellular uptake and intracellular trafficking with chitosan/DNA/poly(gamma-glutamic acid) complexes as a gene delivery vector. Biomaterials. 2011;32(1):239–248. doi:10.1016/j.biomaterials.2010.08.081
  • Deng J, Wen Y, Wang C, et al. Efficient intracellular gene delivery using the formulation composed of poly (L-glutamic acid) grafted polyethylenimine and histone. Pharm Res. 2011;28(4):812–826. doi:10.1007/s11095-010-0335-z
  • Sawada M, Matsumoto M, Sawamoto K. Vascular regulation of adult neurogenesis under physiological and pathological conditions. Front Neurosci. 2014;8:53. doi:10.3389/fnins.2014.00053
  • Maden M. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci. 2007;8(10):755–765. doi:10.1038/nrn2212
  • Saito A, Sugawara A, Uruno A, et al. All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling. Endocrinology. 2007;148(3):1412–1423. doi:10.1210/en.2006-0900
  • Jin Y, Raviv N, Barnett A, Bambakidis NC, Filichia E, Luo Y. The shh signaling pathway is upregulated in multiple cell types in cortical ischemia and influences the outcome of stroke in an animal model. PLoS One. 2015;10(4):e0124657. doi:10.1371/journal.pone.0124657
  • Zhang X, Zhou Y, Li H, et al. Intravenous administration of DPSCs and BDNF improves neurological performance in rats with focal cerebral ischemia. Int J Mol Med. 2018;41(6):3185–3194. doi:10.3892/ijmm.2018.3517
  • Zhang ZG, Zhang L, Tsang W, et al. Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab. 2002;22(4):379–392. doi:10.1097/00004647-200204000-00002
  • Li S, Nih LR, Bachman H, et al. Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. Nat Mater. 2017;16(9):953–961. doi:10.1038/nmat4954
  • Nih LR, Gojgini ST, Carmichael S, Segura T. Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke. Nat Mater. 2018;17(7):642–651. doi:10.1038/s41563-018-0083-8
  • Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011;3(3):a004994–a004994. doi:10.1101/cshperspect.a004994
  • Sun J, Yu L, Huang S, Lai X, Milner R, Li L. Vascular expression of angiopoietin1, alpha5beta1 integrin and tight junction proteins is tightly regulated during vascular remodeling in the post-ischemic brain. Neuroscience. 2017;362:248–256. doi:10.1016/j.neuroscience.2017.08.040
  • Feng Y, Mrksich M. The synergy peptide PHSRN and the adhesion peptide RGD mediate cell adhesion through a common mechanism. Biochemistry. 2004;43(50):15811–15821.
  • Wu CC, Wang LC, Su YT, Wei WY, Tsai KJ. Synthetic alpha5beta1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke. Biomaterials. 2018;185:142–154. doi:10.1016/j.biomaterials.2018.09.014
  • Cui W, Liu R, Jin H, et al. pH gradient difference around ischemic brain tissue can serve as a trigger for delivering polyethylene glycol-conjugated urokinase nanogels. J Control Release. 2016;225:53–63. doi:10.1016/j.jconrel.2016.01.028
  • Luo Y, Yang H, Zhou YF, Hu B. Dual and multi-targeted nanoparticles for site-specific brain drug delivery. J Control Release. 2020;317:195–215. doi:10.1016/j.jconrel.2019.11.037
  • Cheng R, Meng F, Deng C, Klok HA, Zhong Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 2013;34(14):3647–3657. doi:10.1016/j.biomaterials.2013.01.084
  • Hu H, Li Y, Zhou Q, et al. Redox-sensitive hydroxyethyl starch-doxorubicin conjugate for tumor targeted drug delivery. ACS Appl Mater Interfaces. 2016;8(45):30833–30844. doi:10.1021/acsami.6b11932
  • Hu H, Xiao C, Wu H, et al. Nanocolloidosomes with selective drug release for active tumor-targeted imaging-guided photothermal/chemo combination therapy. ACS Appl Mater Interfaces. 2017;9(48):42225–42238. doi:10.1021/acsami.7b14796
  • Esquiva G, Grayston A, Rosell A. Revascularization and endothelial progenitor cells in stroke. Am J Physiol Cell Physiol. 2018;315(5):C664–C674. doi:10.1152/ajpcell.00200.2018
  • Aziz A, Haywood NJ, Cordell PA, et al. Insulin like growth factor-binding protein-1 improves vascular endothelial repair in male mice in the setting of insulin resistance. Endocrinology. 2018;159(2):696–709. doi:10.1210/en.2017-00572
  • Wang H, Yin YG, Huang H, et al. Transplantation of EPCs overexpressing PDGFR-beta promotes vascular repair in the early phase after vascular injury. BMC Cardiovasc Disord. 2016;16(1):179. doi:10.1186/s12872-016-0353-9
  • Wang H, Yin Y, Li W, et al. Over-expression of PDGFR-beta promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway. PLoS One. 2012;7(2):e30503. doi:10.1371/journal.pone.0030503
  • Seto SW, Chang D, Jenkins A, Bensoussan A, Kiat H. Angiogenesis in ischemic stroke and angiogenic effects of Chinese herbal medicine. J Clin Med. 2016;5(6):56. doi:10.3390/jcm5060056
  • Ergul A, Alhusban A, Fagan SC. Angiogenesis: a harmonized target for recovery after stroke. Stroke. 2012;43(8):2270–2274. doi:10.1161/STROKEAHA.111.642710
  • Manoonkitiwongsa PS, Jackson-Friedman C, McMillan PJ, Schultz RL, Lyden PD. Angiogenesis after stroke is correlated with increased numbers of macrophages: the clean-up hypothesis. J Cereb Blood Flow Metab. 2001;21(10):1223–1231. doi:10.1097/00004647-200110000-00011
  • Fang W, Zhai X, Han D, et al. CCR2-dependent monocytes/macrophages exacerbate acute brain injury but promote functional recovery after ischemic stroke in mice. Theranostics. 2018;8(13):3530–3543. doi:10.7150/thno.24475
  • Zong X, Li Y, Liu C, et al. Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization. Theranostics. 2020;10(26):12090–12110. doi:10.7150/thno.51573
  • Jickling GC, Liu D, Stamova B, et al. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab. 2014;34(2):185–199. doi:10.1038/jcbfm.2013.203
  • Villaran RF, de Pablos RM, Arguelles S, et al. The intranigral injection of tissue plasminogen activator induced blood-brain barrier disruption, inflammatory process and degeneration of the dopaminergic system of the rat. Neurotoxicology. 2009;30(3):403–413. doi:10.1016/j.neuro.2009.02.011
  • Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372(9646):1303–1309. doi:10.1016/S0140-6736(08)61339-2
  • Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010;67(2):181–198. doi:10.1016/j.neuron.2010.07.002
  • Sun T, Jiang C. Stimuli-responsive drug delivery systems triggered by intracellular or subcellular microenvironments. Adv Drug Deliv Rev. 2023;196:114773. doi:10.1016/j.addr.2023.114773
  • Zhu W, Huang L, Li Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37. doi:10.1016/j.canlet.2011.10.002
  • Urban N, Guillemot F. Neurogenesis in the embryonic and adult brain: same regulators, different roles. Front Cell Neurosci. 2014;8:396. doi:10.3389/fncel.2014.00396
  • Dibajnia P, Morshead CM. Role of neural precursor cells in promoting repair following stroke. Acta Pharmacol Sin. 2013;34(1):78–90. doi:10.1038/aps.2012.107
  • Huang TT, Zou Y, Corniola R. Oxidative stress and adult neurogenesis--effects of radiation and superoxide dismutase deficiency. Semin Cell Dev Biol. 2012;23(7):738–744. doi:10.1016/j.semcdb.2012.04.003
  • Mizuma A, Yenari MA. Anti-inflammatory targets for the treatment of reperfusion injury in stroke. Front Neurol. 2017;8:467. doi:10.3389/fneur.2017.00467
  • Chelluboina B, Klopfenstein JD, Gujrati M, Rao JS, Veeravalli KK. Temporal regulation of apoptotic and anti-apoptotic molecules after middle cerebral artery occlusion followed by reperfusion. Mol Neurobiol. 2014;49(1):50–65. doi:10.1007/s12035-013-8486-7
  • Carta G, Poddighe L, Serra MP, et al. Preventive effects of resveratrol on endocannabinoid system and synaptic protein modifications in rat cerebral cortex challenged by bilateral common carotid artery occlusion and reperfusion. Int J Mol Sci. 2018;19(2):426. doi:10.3390/ijms19020426
  • Fonseca-Santos B, Satake CY, Calixto GMF, Dos Santos AM, Chorilli M. Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems: structural, rheological, mechanical, textural, and bioadhesive characterization and evaluation of in vivo anti-inflammatory activity. Int J Nanomed. 2017;12:6883–6893. doi:10.2147/IJN.S138629
  • Lu X, Xu H, Sun B, Zhu Z, Zheng D, Li X. Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxide-induced oxidative stress in rat cortical cell culture. Mol Pharm. 2013;10(5):2045–2053. doi:10.1021/mp400056c
  • Barui AK, Jhelum P, Nethi SK, et al. Potential therapeutic application of zinc oxide nanoflowers in the cerebral ischemia rat model through neuritogenic and neuroprotective properties. Bioconjug Chem. 2020;31(3):895–906. doi:10.1021/acs.bioconjchem.0c00030
  • Kim CK, Kim T, Choi IY, et al. Ceria nanoparticles that can protect against ischemic stroke. Angew Chem Int Ed Engl. 2012;51(44):11039–11043. doi:10.1002/anie.201203780
  • Liao J, Li Y, Fan L, et al. Bioactive ceria nanoenzymes target mitochondria in reperfusion injury to treat ischemic stroke. ACS Nano. 2024;2014:1.
  • He L, Huang G, Liu H, Sang C, Liu X, Chen T. Highly bioactive zeolitic imidazolate framework-8-capped nanotherapeutics for efficient reversal of reperfusion-induced injury in ischemic stroke. Sci Adv. 2020;6(12):eaay9751. doi:10.1126/sciadv.aay9751
  • Wang S, Ma F, Huang L, et al. Dl-3-n-Butylphthalide (NBP): a promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets. 2018;17(5):338–347. doi:10.2174/1871527317666180612125843
  • Qin C, Zhou P, Wang L, et al. Dl-3-N-butylphthalide attenuates ischemic reperfusion injury by improving the function of cerebral artery and circulation. J Cereb Blood Flow Metab. 2019;39(10):2011–2021. doi:10.1177/0271678X18776833
  • Yang CS, Guo A, Li Y, Shi K, Shi FD, Li M. Dl-3-n-butylphthalide reduces neurovascular inflammation and ischemic brain injury in mice. Aging Dis. 2019;10(5):964–976. doi:10.14336/AD.2019.0608
  • Yang LC, Li J, Xu SF, et al. L-3-n-butylphthalide promotes neurogenesis and neuroplasticity in cerebral ischemic rats. CNS Neurosci Ther. 2015;21(9):733–741. doi:10.1111/cns.12438
  • Liu S, Shi H, Liu W, Furuichi T, Timmins GS, Liu KJ. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004;24(3):343–349. doi:10.1097/01.WCB.0000110047.43905.01
  • Atsumi S, Higashide W, Liao JC. Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde. Nat Biotechnol. 2009;27(12):1177–1180. doi:10.1038/nbt.1586
  • Xu Y, Ma P, Shah P, Rokas A, Liu Y, Johnson CH. Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature. 2013;495(7439):116–120. doi:10.1038/nature11942
  • Cohen JE, Goldstone AB, Paulsen MJ, et al. An innovative biologic system for photon-powered myocardium in the ischemic heart. Sci Adv. 2017;3(6):e1603078. doi:10.1126/sciadv.1603078
  • Qiao Y, Yang F, Xie T, et al. Engineered algae: a novel oxygen-generating system for effective treatment of hypoxic cancer. Sci Adv. 2020;6(21):eaba5996. doi:10.1126/sciadv.aba5996
  • Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol. 2001;19(4):316–317. doi:10.1038/86684
  • Liu J, Pan L, Shang C, et al. A highly sensitive and selective nanosensor for near-infrared potassium imaging. Sci Adv. 2020;6(16):eaax9757. doi:10.1126/sciadv.aax9757
  • Byrdin M, Jordan P, Krauss N, Fromme P, Stehlik D, Schlodder E. Light harvesting in photosystem I: modeling based on the 2.5-A structure of photosystem I from Synechococcus elongatus. Biophys J. 2002;83(1):433–457. doi:10.1016/S0006-3495(02)75181-3
  • Dau H, Zaharieva I. Principles, efficiency, and blueprint character of solar-energy conversion in photosynthetic water oxidation. Acc Chem Res. 2009;42(12):1861–1870. doi:10.1021/ar900225y
  • Wang F, Deng R, Wang J, et al. Tuning upconversion through energy migration in core-shell nanoparticles. Nat Mater. 2011;10(12):968–973. doi:10.1038/nmat3149
  • Wang J, Wang F, Wang C, Liu Z, Liu X. Single-band upconversion emission in lanthanide-doped KMnF3 nanocrystals. Angew Chem Int Ed Engl. 2011;50(44):10369–10372. doi:10.1002/anie.201104192
  • Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48. doi:10.1016/j.addr.2012.09.037
  • Al-Ahmady ZS, Jasim D, Ahmad SS, et al. Selective liposomal transport through blood brain barrier disruption in ischemic stroke reveals two distinct therapeutic opportunities. ACS Nano. 2019;13(11):12470–12486. doi:10.1021/acsnano.9b01808
  • Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021;20(5):362–383. doi:10.1038/s41573-021-00139-y
  • Li C, Liu K, Liu S, Aerqin Q, Wu X. Role of ginkgolides in the inflammatory immune response of neurological diseases: a review of current literatures. Front Syst Neurosci. 2020;14:45. doi:10.3389/fnsys.2020.00045
  • Wei H, Sun T, Tian Y, Wang K. Ginkgolide B Modulates BDNF expression in acute ischemic stroke. J Korean Neurosurg Soc. 2017;60(4):391–396. doi:10.3340/jkns.2016.1010.018
  • Zheng PD, Mungur R, Zhou HJ, Hassan M, Jiang SN, Zheng JS. Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro. Neural Regen Res. 2018;13(7):1204–1211. doi:10.4103/1673-5374.232476
  • Thid D, Benkoski JJ, Svedhem S, Kasemo B, Gold J. DHA-induced changes of supported lipid membrane morphology. Langmuir. 2007;23(11):5878–5881. doi:10.1021/la700523x
  • Yu WB, Cao L, Zhao YY, Xiao W, Xiao BG. Comparing the role of Ginkgolide B and Ginkgolide K on cultured astrocytes exposed to oxygen‑glucose deprivation. Mol Med Rep. 2018;18(5):4417–4427. doi:10.3892/mmr.2018.9450
  • Liao J, Gong L, Xu Q, et al. Revolutionizing neurocare: biomimetic nanodelivery via cell membranes. Adv Mater;2024. e2402445. doi:10.1002/adma.202402445
  • Jiang Y, Wang R, Wang C, et al. Brain microenvironment responsive and pro-angiogenic extracellular vesicle-hydrogel for promoting neurobehavioral recovery in type 2 diabetic mice after stroke. Adv Healthc Mater. 2022;11(22):e2201150. doi:10.1002/adhm.202201150
  • Bang OY, Kim EH. Mesenchymal stem cell-derived extracellular vesicle therapy for stroke: challenges and progress. Front Neurol. 2019;10:211. doi:10.3389/fneur.2019.00211
  • Reis C, Wilkinson M, Reis H, et al. A look into stem cell therapy: exploring the options for treatment of ischemic stroke. Stem Cells Int. 2017;2017:3267352. doi:10.1155/2017/3267352
  • Sakata H, Niizuma K, Yoshioka H, et al. Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats. J Neurosci. 2012;32(10):3462–3473. doi:10.1523/JNEUROSCI.5686-11.2012
  • Dao M, Tate CC, McGrogan M, Case CC. Comparing the angiogenic potency of naive marrow stromal cells and Notch-transfected marrow stromal cells. J Transl Med. 2013;11:81. doi:10.1186/1479-5876-11-81
  • Noiseux N, Gnecchi M, Lopez-Ilasaca M, et al. Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther. 2006;14(6):840–850. doi:10.1016/j.ymthe.2006.05.016
  • Lu D, Chen B, Liang Z, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabet Res Clin Pract. 2011;92(1):26–36. doi:10.1016/j.diabres.2010.12.010
  • Abdal Dayem A, Lee SB, Kim K, et al. Production of mesenchymal stem cells through stem cell reprogramming. Int J Mol Sci. 2019;20(8):1922. doi:10.3390/ijms20081922
  • Venkat P, Chen J, Chopp M. Exosome-mediated amplification of endogenous brain repair mechanisms and brain and systemic organ interaction in modulating neurological outcome after stroke. J Cereb Blood Flow Metab. 2018;38(12):2165–2178. doi:10.1177/0271678X18782789
  • Zhang ZG, Buller B, Chopp M. Exosomes - beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol. 2019;15(4):193–203. doi:10.1038/s41582-018-0126-4
  • Kishore R, Khan M. More than tiny sacks: stem cell exosomes as cell-free modality for cardiac repair. Circ Res. 2016;118(2):330–343. doi:10.1161/CIRCRESAHA.115.307654
  • Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 2009;8(5):491–500. doi:10.1016/S1474-4422(09)70061-4
  • Jiang X, Suenaga J, Pu H, et al. Post-stroke administration of omega-3 polyunsaturated fatty acids promotes neurovascular restoration after ischemic stroke in mice: efficacy declines with aging. Neurobiol Dis. 2019;126:62–75. doi:10.1016/j.nbd.2018.09.012
  • Fei X, Zhang X, Wang Q, et al. Xijiao dihuang decoction alleviates ischemic brain injury in MCAO rats by regulating inflammation, neurogenesis, and angiogenesis. Evid Based Complement Alternat Med. 2018;2018:5945128. doi:10.1155/2018/5945128
  • Doeppner TR, Herz J, Gorgens A, et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med. 2015;4(10):1131–1143. doi:10.5966/sctm.2015-0078
  • Xin H, Katakowski M, Wang F, et al. MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke. 2017;48(3):747–753. doi:10.1161/STROKEAHA.116.015204
  • Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab. 2013;33(11):1711–1715. doi:10.1038/jcbfm.2013.152
  • Wang C, Borger V, Sardari M, et al. Mesenchymal stromal cell-derived small extracellular vesicles induce ischemic neuroprotection by modulating leukocytes and specifically neutrophils. Stroke. 2020;51(6):1825–1834. doi:10.1161/STROKEAHA.119.028012
  • De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer. 2017;17(8):457–474. doi:10.1038/nrc.2017.51
  • Lee JK, Park SR, Jung BK, et al. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS One. 2013;8(12):e84256. doi:10.1371/journal.pone.0084256
  • Gonzalez-King H, Garcia NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepulveda P. Hypoxia Inducible Factor-1alpha Potentiates Jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells. 2017;35(7):1747–1759. doi:10.1002/stem.2618
  • Kornhuber J, Muller CP, Becker KA, Reichel M, Gulbins E. The ceramide system as a novel antidepressant target. Trends Pharmacol Sci. 2014;35(6):293–304. doi:10.1016/j.tips.2014.04.003
  • Deng X, Yin X, Allan R, et al. Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science. 2008;322(5898):110–115. doi:10.1126/science.1158111
  • Gulbins E, Palmada M, Reichel M, et al. Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs. Nat Med. 2013;19(7):934–938. doi:10.1038/nm.3214
  • Brunkhorst R, Friedlaender F, Ferreiros N, et al. Alterations of the ceramide metabolism in the peri-infarct cortex are independent of the sphingomyelinase pathway and not influenced by the acid sphingomyelinase inhibitor fluoxetine. Neural Plast. 2015;2015:503079.
  • Herr I, Martin-Villalba A, Kurz E, et al. FK506 prevents stroke-induced generation of ceramide and apoptosis signaling. Brain Res. 1999;826(2):210–219. doi:10.1016/S0006-8993(99)01288-3
  • Ohtani R, Tomimoto H, Kondo T, et al. Upregulation of ceramide and its regulating mechanism in a rat model of chronic cerebral ischemia. Brain Res. 2004;1023(1):31–40. doi:10.1016/j.brainres.2004.07.024
  • Yu ZF, Nikolova-Karakashian M, Zhou D, Cheng G, Schuchman EH, Mattson MP. Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. J Mol Neurosci. 2000;15(2):85–97. doi:10.1385/JMN:15:2:85
  • Kanazawa M, Miura M, Toriyabe M, et al. Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats. Sci Rep. 2017;7:42582. doi:10.1038/srep42582
  • Wattananit S, Tornero D, Graubardt N, et al. Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice. J Neurosci. 2016;36(15):4182–4195. doi:10.1523/JNEUROSCI.4317-15.2016
  • Yu Y, Li J, Zhou H, et al. Functional importance of the TGF-beta1/Smad3 signaling pathway in oxygen-glucose-deprived (OGD) microglia and rats with cerebral ischemia. Int J Biol Macromol. 2018;116:537–544. doi:10.1016/j.ijbiomac.2018.04.113
  • Butovsky O, Jedrychowski MP, Moore CS, et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci. 2014;17(1):131–143. doi:10.1038/nn.3599
  • Krueger TEG, Thorek DLJ, Denmeade SR, Isaacs JT, Brennen WN. Concise Review: mesenchymal Stem Cell-Based Drug Delivery: the Good, the Bad, the Ugly, and the Promise. Stem Cells Transl Med. 2018;7(9):651–663. doi:10.1002/sctm.18-0024
  • Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy. 2010;12(5):576–578. doi:10.3109/14653249.2010.507330
  • Tieu A, Slobodian M, Fergusson DA, et al. Methods and efficacy of extracellular vesicles derived from mesenchymal stromal cells in animal models of disease: a preclinical systematic review protocol. Syst Rev. 2019;8(1):322. doi:10.1186/s13643-019-1242-y
  • Go V, Bowley BGE, Pessina MA, et al. Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys. Geroscience. 2020;42(1):1–17. doi:10.1007/s11357-019-00115-w
  • Webb RL, Kaiser EE, Scoville SL, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl Stroke Res. 2018;9(5):530–539. doi:10.1007/s12975-017-0599-2
  • Anderson JD, Johansson HJ, Graham CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cells. 2016;34(3):601–613. doi:10.1002/stem.2298
  • Zheng X, Zhang L, Kuang Y, et al. Extracellular vesicles derived from neural progenitor cells--a preclinical evaluation for stroke treatment in mice. Transl Stroke Res. 2021;12(1):185–203. doi:10.1007/s12975-020-00814-z
  • Yu Z, Cai Y, Deng M, et al. Fat extract promotes angiogenesis in a murine model of limb ischemia: a novel cell-free therapeutic strategy. Stem Cell Res Ther. 2018;9(1):294. doi:10.1186/s13287-018-1014-y
  • Zheng H, Yu Z, Deng M, et al. Fat extract improves fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative activities. Stem Cell Res Ther. 2019;10(1):174. doi:10.1186/s13287-019-1290-1
  • Dong X, Gao J, Zhang CY, Hayworth C, Frank M, Wang Z. Neutrophil membrane-derived nanovesicles alleviate inflammation to protect mouse brain injury from ischemic stroke. ACS Nano. 2019;13(2):1272–1283. doi:10.1021/acsnano.8b06572
  • Dehaini D, Wei X, Fang RH, et al. Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization. Adv Mater. 2017;29(16). doi:10.1002/adma.201606209
  • Li M, Li J, Chen J, et al. Platelet membrane biomimetic magnetic nanocarriers for targeted delivery and in situ generation of nitric oxide in early ischemic stroke. ACS Nano. 2020;14(2):2024–2035. doi:10.1021/acsnano.9b08587
  • Xu L, Chen Y, Jin Q, et al. Biomimetic PLGA microbubbles coated with platelet membranes for early detection of myocardial ischaemia-reperfusion injury. Mol Pharm. 2021;18(8):2974–2985. doi:10.1021/acs.molpharmaceut.1c00145
  • Parvez S, Kaushik M, Ali M, et al. Dodging blood brain barrier with ”nano” warriors: novel strategy against ischemic stroke. Theranostics. 2022;12(2):689–719. doi:10.7150/thno.64806
  • Sri Kanaka Durga Vijayalakshmi G, Puvvada N. Recent advances in chemically engineered nanostructures impact on ischemic stroke treatment. ACS Omega. 2023;8(48):45188–45207. doi:10.1021/acsomega.3c06228
  • Li C, Sun T, Jiang C. Recent advances in nanomedicines for the treatment of ischemic stroke. Acta Pharm Sin B. 2021;11(7):1767–1788. doi:10.1016/j.apsb.2020.11.019
  • Wang Z, Zhao Y, Jiang Y, et al. Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system. Sci Rep. 2015;5:12651. doi:10.1038/srep12651
  • Lv W, Xu J, Wang X, et al. Bioengineered boronic ester modified dextran polymer nanoparticles as reactive oxygen species responsive nanocarrier for ischemic stroke treatment. ACS Nano. 2018;12(6):5417–5426. doi:10.1021/acsnano.8b00477
  • Bao Q, Hu P, Xu Y, et al. Simultaneous blood-brain barrier crossing and protection for stroke treatment based on edaravone-loaded ceria nanoparticles. ACS Nano. 2018;12(7):6794–6805. doi:10.1021/acsnano.8b01994
  • Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev. 2012;64(7):686–700. doi:10.1016/j.addr.2011.10.007
  • Saraiva C, Praca C, Ferreira R, Santos L, Ferreira L, Bernardino L. Bernardino, Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release. 2016;235:34–47. doi:10.1016/j.jconrel.2016.05.044
  • Tian T, Zhang HX, He CP, et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 2018;150:137–149. doi:10.1016/j.biomaterials.2017.10.012