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Nanoparticles Treat Ischemic Stroke by Responding to Stroke Microenvironment

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Abstract

The efficacy and safety of treating ischemic stroke is still a challenging problem at this stage. Ischemic stroke has a special stroke microenvironment. In recent years, improving stroke microenvironment has become a new idea for treating ischemic stroke. At the same time, nanoparticles have unique physical and chemical properties and significant advantages in studying ischemic stroke. Therefore, in recent years, researchers have designed various types of nanoparticles in response to stroke microenvironment to treat ischemic stroke. In this review, we summarized and analyzed the ischemic areas targeted by nanoparticles in response to reactive oxygen species, pH, high expression of receptors in the blood–brain barrier, enrichment of molecules in the stroke microenvironment, light, magnetic harmony, and other stimuli. We analyze its advantages and disadvantages and look forward to the development prospect of this field. Hope to provide strategies for better treatment of ischemic stroke.

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References

  1. Zhou, M., Wang, H., Zeng, X., Yin, P., Zhu, J., Chen, W., Li, X., Wang, L., Wang, L., Liu, Y., Liu, J., Zhang, M., Qi, J., Yu, S., Afshin, A., Gakidou, E., Glenn, S., Krish, V. S., Miller-Petrie, M. K., … Liang, X. (2019). Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 394(10204), 1145–1158.

    PubMed  PubMed Central  Google Scholar 

  2. Benjamin, E. J., Virani, S. S., Callaway, C. W., Chamberlain, A. M., Chang, A. R., Cheng, S., Chiuve, S. E., Cushman, M., Delling, F. N., Deo, R., de Ferranti, S. D., Ferguson, J. F., Fornage, M., Gillespie, C., Isasi, C. R., Jiménez, M. C., Jordan, L. C., Judd, S. E., Lackland, D., … Muntner, P. (2018). Heart Disease and stroke statistics-2018 update: A report from the American Heart Association. Circulation, 137(12), e67–e492.

    PubMed  Google Scholar 

  3. Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., de Ferranti, S. D., Floyd, J., Fornage, M., Gillespie, C., Isasi, C. R., Jiménez, M. C., Jordan, L. C., Judd, S. E., Lackland, D., Lichtman, J. H., Lisabeth, L., Liu, S., Longenecker, C. T., … Muntner, P. (2017). Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation, 135(10), e146–e603.

    PubMed  PubMed Central  Google Scholar 

  4. Arumugam, T. V., Baik, S. H., Balaganapathy, P., Sobey, C. G., Mattson, M. P., & Jo, D. G. (2018). Notch signaling and neuronal death in stroke. Progress in Neurobiology, 165–167, 103–116.

    PubMed  PubMed Central  Google Scholar 

  5. Ham, P. B., 3rd, Raju, R., (2017). Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol, 157, 92-116

  6. He, Q., Ma, Y., Liu, J., Zhang, D., Ren, J., Zhao, R., Chang, J., Guo, Z. N., & Yang, Y. (2021). Biological functions and regulatory mechanisms of hypoxia-inducible factor-1α in ischemic stroke. Frontiers in Immunology, 12, 801985.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Khaja, A. M., & Grotta, J. C. (2007). Established treatments for acute ischaemic stroke. Lancet, 369(9558), 319–330.

    CAS  PubMed  Google Scholar 

  8. Sacco, R. L., Chong, J. Y., Prabhakaran, S., & Elkind, M. S. (2007). Experimental treatments for acute ischaemic stroke. Lancet, 369(9558), 331–341.

    CAS  PubMed  Google Scholar 

  9. Mizuma, A., You, J. S., & Yenari, M. A. (2018). Targeting reperfusion injury in the age of mechanical thrombectomy. Stroke, 49(7), 1796–1802.

    PubMed  PubMed Central  Google Scholar 

  10. Jones, A. R., & Shusta, E. V. (2007). Blood-brain barrier transport of therapeutics via receptor-mediation. Pharmaceutical Research, 24(9), 1759–1771.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Patel, T., Zhou, J., Piepmeier, J. M., & Saltzman, W. M. (2012). Polymeric nanoparticles for drug delivery to the central nervous system. Advanced Drug Delivery Reviews, 64(7), 701–705.

    CAS  PubMed  Google Scholar 

  12. Lobatto, M. E., Fuster, V., Fayad, Z. A., & Mulder, W. J. (2011). Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nature Reviews. Drug Discovery, 10(11), 835–852.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Thomas, C. R., Ferris, D. P., Lee, J. H., Choi, E., Cho, M. H., Kim, E. S., Stoddart, J. F., Shin, J. S., Cheon, J., & Zink, J. I. (2010). Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. Journal of the American Chemical Society, 132(31), 10623–10625.

    CAS  PubMed  Google Scholar 

  14. Zhang, N. N., Shen, X., Liu, K., Nie, Z., & Kumacheva, E. (2022). Polymer-tethered nanoparticles: From surface engineering to directional self-assembly. Accounts of Chemical Research, 55(11), 1503–1513.

    CAS  PubMed  Google Scholar 

  15. Whitesides, G. M. (2003). The ‘right’ size in nanobiotechnology. Nature Biotechnology, 21(10), 1161–1165.

    CAS  PubMed  Google Scholar 

  16. Morachis, J. M., Mahmoud, E. A., & Almutairi, A. (2012). Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacological Reviews, 64(3), 505–519.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Algar, W. R., Massey, M., Rees, K., Higgins, R., Krause, K. D., Darwish, G. H., Peveler, W. J., Xiao, Z., Tsai, H. Y., Gupta, R., Lix, K., Tran, M. V., & Kim, H. (2021). Photoluminescent nanoparticles for chemical and biological analysis and imaging. Chemical Reviews, 121(15), 9243–9358.

    CAS  PubMed  Google Scholar 

  18. Kim, K. S., Suzuki, K., Cho, H., Youn, Y. S., & Bae, Y. H. (2018). Oral nanoparticles exhibit specific high-efficiency intestinal uptake and lymphatic transport. ACS Nano, 12(9), 8893–8900.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Hutter, E., & Maysinger, D. (2011). Gold nanoparticles and quantum dots for bioimaging. Microscopy Research and Technique, 74(7), 592–604.

    CAS  PubMed  Google Scholar 

  20. Bhumkar, D. R., Joshi, H. M., Sastry, M., & Pokharkar, V. B. (2007). Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin. Pharmaceutical Research, 24(8), 1415–1426.

    CAS  PubMed  Google Scholar 

  21. Phillips, R. L., Miranda, O. R., You, C. C., Rotello, V. M., & Bunz, U. H. (2008). Rapid and efficient identification of bacteria using gold-nanoparticle-poly(para-phenyleneethynylene) constructs. Angewandte Chemie (International ed. in English), 47(14), 2590–2594.

    CAS  PubMed  Google Scholar 

  22. Kairdolf, B. A., Qian, X., & Nie, S. (2017). Bioconjugated nanoparticles for biosensing, in vivo imaging, and medical diagnostics. Analytical Chemistry, 89(2), 1015–1031.

    CAS  PubMed  Google Scholar 

  23. Saha, K., Agasti, S. S., Kim, C., Li, X., & Rotello, V. M. (2012). Gold nanoparticles in chemical and biological sensing. Chemical Reviews, 112(5), 2739–2779.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Kaviarasi, S., Yuba, E., Harada, A., & Krishnan, U. M. (2019). Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia. Journal of Controlled Release, 300, 22–45.

    CAS  PubMed  Google Scholar 

  25. Nozohouri, S., Sifat, A. E., Vaidya, B., & Abbruscato, T. J. (2020). Novel approaches for the delivery of therapeutics in ischemic stroke. Drug Discovery Today, 25(3), 535–551.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Bharadwaj, V. N.; Nguyen, D. T.; Kodibagkar, V. D.; Stabenfeldt, S. E., Nanoparticle-based therapeutics for brain injury. Adv Healthc Mater 2018, 7 (1).

  27. Sahay, G., Alakhova, D. Y., & Kabanov, A. V. (2010). Endocytosis of nanomedicines. Journal of Controlled Release, 145(3), 182–195.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W. (2021). Strategies for delivering therapeutics across the blood-brain barrier. Nature Reviews. Drug Discovery, 20(5), 362–383.

    CAS  PubMed  Google Scholar 

  29. Sandoval, K. E., & Witt, K. A. (2008). Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiology of Diseases, 32(2), 200–219.

    CAS  Google Scholar 

  30. Jin, L., Zhu, Z., Hong, L., Qian, Z., Wang, F., & Mao, Z. (2023). ROS-responsive 18β-glycyrrhetic acid-conjugated polymeric nanoparticles mediate neuroprotection in ischemic stroke through HMGB1 inhibition and microglia polarization regulation. Bioact Mater, 19, 38–49.

    CAS  PubMed  Google Scholar 

  31. Zhang, S., Peng, B., Chen, Z., Yu, J., Deng, G., Bao, Y., Ma, C., Du, F., Sheu, W. C., Kimberly, W. T., Simard, J. M., Coman, D., Chen, Q., Hyder, F., Zhou, J., & Sheth, K. N. (2022). Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery. Bioact Mater, 16, 57–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Shen, Z., Liu, T., Li, Y., Lau, J., Yang, Z., Fan, W., Zhou, Z., Shi, C., Ke, C., Bregadze, V. I., Mandal, S. K., Liu, Y., Li, Z., Xue, T., Zhu, G., Munasinghe, J., Niu, G., Wu, A., & Chen, X. (2018). Fenton-reaction-acceleratable magnetic nanoparticles for ferroptosis therapy of orthotopic brain tumors. ACS Nano, 12(11), 11355–11365.

    CAS  PubMed  Google Scholar 

  33. Bao, Q., Hu, P., Xu, Y., Cheng, T., Wei, C., Pan, L., & Shi, J. (2018). Simultaneous blood-brain barrier crossing and protection for stroke treatment based on edaravone-loaded ceria nanoparticles. ACS Nano, 12(7), 6794–6805.

    CAS  PubMed  Google Scholar 

  34. Kim, H. Y., Kim, T. J., Kang, L., Kim, Y. J., Kang, M. K., Kim, J., Ryu, J. H., Hyeon, T., Yoon, B. W., Ko, S. B., & Kim, B. S. (2020). Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke. Biomaterials, 243, 119942.

    CAS  PubMed  Google Scholar 

  35. Correa-Paz, C., Navarro Poupard, M. F., Polo, E., Rodríguez-Pérez, M., Migliavacca, M., Iglesias-Rey, R., Ouro, A., Maqueda, E., Hervella, P., Sobrino, T., Castillo, J., Del Pino, P., Pelaz, B., & Campos, F. (2022). Sonosensitive capsules for brain thrombolysis increase ischemic damage in a stroke model. J Nanobiotechnology, 20(1), 46.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Yu, W., Yin, N., Yang, Y., Xuan, C., Liu, X., Liu, W., Zhang, Z., Zhang, K., Liu, J., & Shi, J. (2022). Rescuing ischemic stroke by biomimetic nanovesicles through accelerated thrombolysis and sequential ischemia-reperfusion protection. Acta Biomaterialia, 140, 625–640.

    CAS  PubMed  Google Scholar 

  37. Chamorro, Á., Dirnagl, U., Urra, X., & Planas, A. M. (2016). Neuroprotection in acute stroke: Targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurology, 15(8), 869–881.

    CAS  PubMed  Google Scholar 

  38. Minnerup, J., Sutherland, B. A., Buchan, A. M., & Kleinschnitz, C. (2012). Neuroprotection for stroke: Current status and future perspectives. International Journal of Molecular Sciences, 13(9), 11753–11772.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. de Los Ríos la Rosa, F.; Khoury, J.; Kissela, B. M.; Flaherty, M. L.; Alwell, K.; Moomaw, C. J.; Khatri, P.; Adeoye, O.; Woo, D.; Ferioli, S.; Kleindorfer, D. O., (2012). Eligibility for intravenous recombinant tissue-type plasminogen activator within a population: The effect of the European Cooperative Acute Stroke Study (ECASS) III Trial. Stroke, 43 (6), 1591–5.

  40. Fu, Y., Liu, Q., Anrather, J., & Shi, F. D. (2015). Immune interventions in stroke. Nature Reviews. Neurology, 11(9), 524–535.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Mracsko, E., Javidi, E., Na, S. Y., Kahn, A., Liesz, A., & Veltkamp, R. (2014). Leukocyte invasion of the brain after experimental intracerebral hemorrhage in mice. Stroke, 45(7), 2107–2114.

    PubMed  Google Scholar 

  42. Kleinschnitz, C., Kraft, P., Dreykluft, A., Hagedorn, I., Göbel, K., Schuhmann, M. K., Langhauser, F., Helluy, X., Schwarz, T., Bittner, S., Mayer, C. T., Brede, M., Varallyay, C., Pham, M., Bendszus, M., Jakob, P., Magnus, T., Meuth, S. G., Iwakura, Y., … Wiendl, H. (2013). Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood, 121(4), 679–691.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Kanazawa, M., Ninomiya, I., Hatakeyama, M., Takahashi, T., Shimohata, T., (2017). Microglia and monocytes/macrophages polarization reveal novel therapeutic mechanism against stroke. Int J Mol Sci, 18 (10).

  44. Ma, Y., Wang, J., Wang, Y., & Yang, G. Y. (2017). The biphasic function of microglia in ischemic stroke. Progress in Neurobiology, 157, 247–272.

    CAS  PubMed  Google Scholar 

  45. Tang, C., Wang, C., Zhang, Y., Xue, L., Li, Y., Ju, C., & Zhang, C. (2019). Recognition, intervention, and monitoring of neutrophils in acute ischemic stroke. Nano Letters, 19(7), 4470–4477.

    ADS  CAS  PubMed  Google Scholar 

  46. Mai, C. L., Tan, Z., Xu, Y. N., Zhang, J. J., Huang, Z. H., Wang, D., Zhang, H., Gui, W. S., Zhang, J., Lin, Z. J., Meng, Y. T., Wei, X., Jie, Y. T., Grace, P. M., Wu, L. J., Zhou, L. J., & Liu, X. G. (2021). CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain. Theranostics, 11(3), 1059–1078.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Hubert, V., Hristovska, I., Karpati, S., Benkeder, S., Dey, A., Dumot, C., Amaz, C., Chounlamountri, N., Watrin, C., Comte, J. C., Chauveau, F., Brun, E., Marche, P., Lerouge, F., Parola, S., Berthezène, Y., Vorup-Jensen, T., Pascual, O., & Wiart, M. (2021). Multimodal imaging with nanogd reveals spatiotemporal features of neuroinflammation after experimental stroke. Adv Sci (Weinh), 8(17), e2101433.

    PubMed  Google Scholar 

  48. Wang, J., Su, Q., Lv, Q., Cai, B., Xiaohalati, X., Wang, G., Wang, Z., & Wang, L. (2021). Oxygen-generating cyanobacteria powered by upconversion-nanoparticles-converted near-infrared light for ischemic stroke treatment. Nano Letters, 21(11), 4654–4665.

    ADS  CAS  PubMed  Google Scholar 

  49. Powers, W. J., Rabinstein, A. A., Ackerson, T., Adeoye, O. M., Bambakidis, N. C., Becker, K., Biller, J., Brown, M., Demaerschalk, B. M., Hoh, B., Jauch, E. C., Kidwell, C. S., Leslie-Mazwi, T. M., Ovbiagele, B., Scott, P. A., Sheth, K. N., Southerland, A. M., Summers, D. V., & Tirschwell, D. L. (2019). 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, 50(12), e344–e418.

    PubMed  Google Scholar 

  50. Li, J., Dirisala, A., Ge, Z., Wang, Y., Yin, W., Ke, W., Toh, K., Xie, J., Matsumoto, Y., Anraku, Y., Osada, K., & Kataoka, K. (2017). Therapeutic vesicular nanoreactors with tumor-specific activation and self-destruction for synergistic tumor ablation. Angewandte Chemie (International ed. in English), 56(45), 14025–14030.

    CAS  PubMed  Google Scholar 

  51. Li, J., Anraku, Y., & Kataoka, K. (2020). Self-boosting catalytic nanoreactors integrated with triggerable crosslinking membrane networks for initiation of immunogenic cell death by pyroptosis. Angewandte Chemie (International ed. in English), 59(32), 13526–13530.

    CAS  PubMed  Google Scholar 

  52. Yang, G., Song, J., & Zhang, J. (2020). Biomimetic and bioresponsive nanotherapies for inflammatory vascular diseases. Nanomedicine (London, England), 15(20), 1917–1921.

    CAS  PubMed  Google Scholar 

  53. Dou, Y., Li, C., Li, L., Guo, J., & Zhang, J. (2020). Bioresponsive drug delivery systems for the treatment of inflammatory diseases. Journal of Controlled Release, 327, 641–666.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Cheng, J., Zhang, R., Li, C., Tao, H., Dou, Y., Wang, Y., Hu, H., & Zhang, J. (2018). A targeting nanotherapy for abdominal aortic aneurysms. Journal of the American College of Cardiology, 72(21), 2591–2605.

    CAS  PubMed  Google Scholar 

  55. Yuan, J., Li, L., Yang, Q., Ran, H., Wang, J., Hu, K., Pu, W., Huang, J., Wen, L., Zhou, L., Jiang, Y., Xiong, X., Zhang, J., & Zhou, Z. (2021). Targeted treatment of ischemic stroke by bioactive nanoparticle-derived reactive oxygen species responsive and inflammation-resolving nanotherapies. ACS Nano, 15(10), 16076–16094.

    CAS  PubMed  Google Scholar 

  56. Lv, W., Xu, J., Wang, X., Li, X., Xu, Q., & Xin, H. (2018). Bioengineered boronic ester modified dextran polymer nanoparticles as reactive oxygen species responsive nanocarrier for ischemic stroke treatment. ACS Nano, 12(6), 5417–5426.

    CAS  PubMed  Google Scholar 

  57. Hong, H. Y., Choi, J. S., Kim, Y. J., Lee, H. Y., Kwak, W., Yoo, J., Lee, J. T., Kwon, T. H., Kim, I. S., Han, H. S., & Lee, B. H. (2008). Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display. Journal of Controlled Release, 131(3), 167–172.

    CAS  PubMed  Google Scholar 

  58. Zhao, Y., Jiang, Y., Lv, W., Wang, Z., Lv, L., Wang, B., Liu, X., Liu, Y., Hu, Q., Sun, W., Xu, Q., Xin, H., & Gu, Z. (2016). Dual targeted nanocarrier for brain ischemic stroke treatment. Journal of Controlled Release, 233, 64–71.

    CAS  PubMed  Google Scholar 

  59. Chen, Y., Brennan-Minnella, A. M., Sheth, S., El-Benna, J., & Swanson, R. A. (2015). Tat-NR2B9c prevents excitotoxic neuronal superoxide production. Journal of Cerebral Blood Flow and Metabolism, 35(5), 739–742.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Srejic, L. R., Hutchison, W. D., & Aarts, M. M. (2013). Uncoupling PSD-95 interactions leads to rapid recovery of cortical function after focal stroke. Journal of Cerebral Blood Flow and Metabolism, 33(12), 1937–1943.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Hacke, W., Kaste, M., Bluhmki, E., Brozman, M., Dávalos, A., Guidetti, D., Larrue, V., Lees, K. R., Medeghri, Z., Machnig, T., Schneider, D., von Kummer, R., Wahlgren, N., & Toni, D. (2008). Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med, 359(13), 1317–29.

    CAS  PubMed  Google Scholar 

  62. Larrue, V., von Kummer, R. R., Müller, A., & Bluhmki, E. (2001). Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: A secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke, 32(2), 438–441.

    CAS  PubMed  Google Scholar 

  63. Kanazawa, M., Takahashi, T., Nishizawa, M., & Shimohata, T. (2017). Therapeutic strategies to attenuate hemorrhagic transformation after tissue plasminogen activator treatment for acute ischemic stroke. Journal of Atherosclerosis and Thrombosis, 24(3), 240–253.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Granger, D. N., & Kvietys, P. R. (2015). Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biology, 6, 524–551.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Faraci, F. M. (2006). Reactive oxygen species: Influence on cerebral vascular tone. J Appl Physiol (1985), 100(2), 739–43.

    MathSciNet  CAS  PubMed  Google Scholar 

  66. Mei, T., Kim, A., Vong, L. B., Marushima, A., Puentes, S., Matsumaru, Y., Matsumura, A., & Nagasaki, Y. (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.

    CAS  PubMed  Google Scholar 

  67. Palma-Tortosa, S., Tornero, D., Grønning Hansen, M., Monni, E., Hajy, M., Kartsivadze, S., Aktay, S., Tsupykov, O., Parmar, M., Deisseroth, K., Skibo, G., Lindvall, O., & Kokaia, Z. (2020). Activity in grafted human iPS cell-derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior. Proc Natl Acad Sci U S A, 117(16), 9094–9100.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rossi, F., & Cattaneo, E. (2002). Opinion: Neural stem cell therapy for neurological diseases: Dreams and reality. Nature Reviews Neuroscience, 3(5), 401–409.

    CAS  PubMed  Google Scholar 

  69. Lin, B., Lu, L., Wang, Y., Zhang, Q., Wang, Z., Cheng, G., Duan, X., Zhang, F., Xie, M., Le, H., Shuai, X., & Shen, J. (2021). Nanomedicine directs neuronal differentiation of neural stem cells via silencing long noncoding RNA for stroke therapy. Nano Letters, 21(1), 806–815.

    ADS  CAS  PubMed  Google Scholar 

  70. Yoo, A. S., Staahl, B. T., Chen, L., & Crabtree, G. R. (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature, 460(7255), 642–646.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  71. Makeyev, E. V., Zhang, J., Carrasco, M. A., & Maniatis, T. (2007). The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Molecular Cell, 27(3), 435–448.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Saraiva, C., Paiva, J., Santos, T., Ferreira, L., & Bernardino, L. (2016). MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. Journal of Controlled Release, 235, 291–305.

    CAS  PubMed  Google Scholar 

  73. Farh, K. K., Grimson, A., Jan, C., Lewis, B. P., Johnston, W. K., Lim, L. P., Burge, C. B., & Bartel, D. P. (2005). The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science, 310(5755), 1817–1821.

    ADS  CAS  PubMed  Google Scholar 

  74. Xu, X. H., Yuan, T. J., Dad, H. A., Shi, M. Y., Huang, Y. Y., Jiang, Z. H., & Peng, L. H. (2021). Plant exosomes as novel nanoplatforms for MicroRNA transfer stimulate neural differentiation of stem cells in vitro and in vivo. Nano Letters, 21(19), 8151–8159.

    ADS  CAS  PubMed  Google Scholar 

  75. Zhang, J., Chen, C., Fu, H., Yu, J., Sun, Y., Huang, H., Tang, Y., Shen, N., & Duan, Y. (2020). MicroRNA-125a-loaded polymeric nanoparticles alleviate systemic lupus erythematosus by restoring effector/regulatory t cells balance. ACS Nano, 14(4), 4414–4429.

    CAS  PubMed  Google Scholar 

  76. Saraiva, C., Talhada, D., Rai, A., Ferreira, R., Ferreira, L., Bernardino, L., & Ruscher, K. (2018). MicroRNA-124-loaded nanoparticles increase survival and neuronal differentiation of neural stem cells in vitro but do not contribute to stroke outcome in vivo. PLoS ONE, 13(3), e0193609.

    PubMed  PubMed Central  Google Scholar 

  77. Yang, H., Han, M., Li, J., Ke, H., Kong, Y., Wang, W., Wang, L., Ma, W., Qiu, J., Wang, X., Xin, T., & Liu, H. (2022). Delivery of miRNAs through metal-organic framework nanoparticles for assisting neural stem cell therapy for ischemic stroke. ACS Nano, 16(9), 14503–14516.

    CAS  PubMed  Google Scholar 

  78. Lo, E. H., Dalkara, T., & Moskowitz, M. A. (2003). Mechanisms, challenges and opportunities in stroke. Nature Reviews Neuroscience, 4(5), 399–415.

    CAS  PubMed  Google Scholar 

  79. Becher, B., Spath, S., & Goverman, J. (2017). Cytokine networks in neuroinflammation. Nature Reviews Immunology, 17(1), 49–59.

    CAS  PubMed  Google Scholar 

  80. Iadecola, C., & Anrather, J. (2011). The immunology of stroke: From mechanisms to translation. Nature Medicine, 17(7), 796–808.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Shichita, T., Sakaguchi, R., Suzuki, M., & Yoshimura, A. (2012). Post-ischemic inflammation in the brain. Frontiers in Immunology, 3, 132.

    PubMed  PubMed Central  Google Scholar 

  82. Pan, J., Konstas, A. A., Bateman, B., Ortolano, G. A., & Pile-Spellman, J. (2007). Reperfusion injury following cerebral ischemia: Pathophysiology, MR imaging, and potential therapies. Neuroradiology, 49(2), 93–102.

    PubMed  Google Scholar 

  83. Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2012). Cell biology of ischemia/reperfusion injury. International Review of Cell and Molecular Biology, 298, 229–317.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Lakhan, S. E., Kirchgessner, A., & Hofer, M. (2009). Inflammatory mechanisms in ischemic stroke: Therapeutic approaches. Journal of Translational Medicine, 7, 97.

    PubMed  PubMed Central  Google Scholar 

  85. Gautier, S., Ouk, T., Petrault, O., Caron, J., & Bordet, R. (2009). Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia. British Journal of Pharmacology, 156(4), 673–679.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Khan, M. M., Motto, D. G., Lentz, S. R., & Chauhan, A. K. (2012). ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice. Journal of Thrombosis and Haemostasis, 10(8), 1665–1671.

    CAS  PubMed  Google Scholar 

  87. Vinten-Johansen, J. (2004). Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovascular Research, 61(3), 481–497.

    CAS  PubMed  Google Scholar 

  88. Fulurija, A., Ashman, R. B., & Papadimitriou, J. M. (1996). Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance. Microbiology (Reading), 142(Pt 12), 3487–3496.

    CAS  PubMed  Google Scholar 

  89. Jaeger, B. N., Donadieu, J., Cognet, C., Bernat, C., Ordoñez-Rueda, D., Barlogis, V., Mahlaoui, N., Fenis, A., Narni-Mancinelli, E., Beaupain, B., Bellanné-Chantelot, C., Bajénoff, M., Malissen, B., Malissen, M., Vivier, E., & Ugolini, S. (2012). Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. Journal of Experimental Medicine, 209(3), 565–580.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews Immunology, 13(3), 159–175.

    CAS  PubMed  Google Scholar 

  91. Spite, M., Norling, L. V., Summers, L., Yang, R., Cooper, D., Petasis, N. A., Flower, R. J., Perretti, M., & Serhan, C. N. (2009). Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature, 461(7268), 1287–1291.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Chiang, N., Dalli, J., Colas, R. A., & Serhan, C. N. (2015). Identification of resolvin D2 receptor mediating resolution of infections and organ protection. Journal of Experimental Medicine, 212(8), 1203–1217.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Dong, X., Gao, J., Zhang, C. Y., Hayworth, C., Frank, M., & Wang, Z. (2019). Neutrophil membrane-derived nanovesicles alleviate inflammation to protect mouse brain injury from ischemic stroke. ACS Nano, 13(2), 1272–1283.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Liu, S., Shi, H., Liu, W., Furuichi, T., Timmins, G. S., & Liu, K. J. (2004). Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. Journal of Cerebral Blood Flow and Metabolism, 24(3), 343–349.

    CAS  PubMed  Google Scholar 

  95. Saxena, R., Wijnhoud, A. D., Carton, H., Hacke, W., Kaste, M., Przybelski, R. J., Stern, K. N., & Koudstaal, P. J. (1999). Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke, 30(5), 993–996.

    CAS  PubMed  Google Scholar 

  96. Deuchar, G. A., Brennan, D., Holmes, W. M., Shaw, M., Macrae, I. M., & Santosh, C. (2018). Perfluorocarbon enhanced glasgow oxygen level dependent (GOLD) magnetic resonance metabolic imaging identifies the penumbra following acute ischemic stroke. Theranostics, 8(6), 1706–1722.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Kakehata, J., Yamaguchi, T., Togashi, H., Sakuma, I., Otani, H., Morimoto, Y., & Yoshioka, M. (2010). Therapeutic potentials of an artificial oxygen-carrier, liposome-encapsulated hemoglobin, for ischemia/reperfusion-induced cerebral dysfunction in rats. Journal of Pharmacological Sciences, 114(2), 189–197.

    CAS  PubMed  Google Scholar 

  98. Atsumi, S., Higashide, W., & Liao, J. C. (2009). Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde. Nature Biotechnology, 27(12), 1177–1180.

    CAS  PubMed  Google Scholar 

  99. Cohen, J. E., Goldstone, A. B., Paulsen, M. J., Shudo, Y., Steele, A. N., Edwards, B. B., Patel, J. B., MacArthur, J. W., Jr., Hopkins, M. S., Burnett, C. E., Jaatinen, K. J., Thakore, A. D., Farry, J. M., Truong, V. N., Bourdillon, A. T., Stapleton, L. M., Eskandari, A., Fairman, A. S., Hiesinger, W., … Woo, Y. J. (2017). An innovative biologic system for photon-powered myocardium in the ischemic heart. Sci Adv, 3(6), e1603078.

    ADS  PubMed  PubMed Central  Google Scholar 

  100. Qiao, Y.; Yang, F.; Xie, T.; Du, Z.; Zhong, D.; Qi, Y.; Li, Y.; Li, W.; Lu, Z.; Rao, J.; Sun, Y.; Zhou, M., Engineered algae: A novel oxygen-generating system for effective treatment of hypoxic cancer. Sci Adv 2020, 6 (21), eaba5996.

  101. Wang, F., Deng, R., Wang, J., Wang, Q., Han, Y., Zhu, H., Chen, X., & Liu, X. (2011). Tuning upconversion through energy migration in core-shell nanoparticles. Nature Materials, 10(12), 968–973.

    ADS  CAS  PubMed  Google Scholar 

  102. Wang, J., Wang, F., Wang, C., Liu, Z., & Liu, X. (2011). Single-band upconversion emission in lanthanide-doped KMnF3 nanocrystals. Angewandte Chemie (International ed. in English), 50(44), 10369–10372.

    CAS  PubMed  Google Scholar 

  103. Jin, R., Yang, G., & Li, G. (2010). Inflammatory mechanisms in ischemic stroke: Role of inflammatory cells. Journal of Leukocyte Biology, 87(5), 779–789.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Zhang, T., Lee, Y. W., Rui, Y. F., Cheng, T. Y., Jiang, X. H., & Li, G. (2013). Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Research & Therapy, 4(3), 70.

    ADS  CAS  Google Scholar 

  105. Gu, Y., Zhang, Y., Bi, Y., Liu, J., Tan, B., Gong, M., Li, T., & Chen, J. (2015). Mesenchymal stem cells suppress neuronal apoptosis and decrease IL-10 release via the TLR2/NFκB pathway in rats with hypoxic-ischemic brain damage. Molecular Brain, 8(1), 65.

    PubMed  PubMed Central  Google Scholar 

  106. Bhang, S. H., Lee, Y. E., Cho, S. W., Shim, J. W., Lee, S. H., Choi, C. Y., Chang, J. W., & Kim, B. S. (2007). Basic fibroblast growth factor promotes bone marrow stromal cell transplantation-mediated neural regeneration in traumatic brain injury. Biochemical and Biophysical Research Communications, 359(1), 40–45.

    CAS  PubMed  Google Scholar 

  107. Zhang, R., Liu, Y., Yan, K., Chen, L., Chen, X. R., Li, P., Chen, F. F., & Jiang, X. D. (2013). Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. Journal of Neuroinflammation, 10, 106.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Eggenhofer, E., Luk, F., Dahlke, M. H., & Hoogduijn, M. J. (2014). The life and fate of mesenchymal stem cells. Frontiers in Immunology, 5, 148.

    PubMed  PubMed Central  Google Scholar 

  109. Smyth, T., Kullberg, M., Malik, N., Smith-Jones, P., Graner, M. W., & Anchordoquy, T. J. (2015). Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. Journal of Controlled Release, 199, 145–155.

    CAS  PubMed  Google Scholar 

  110. Zhu, X., Badawi, M., Pomeroy, S., Sutaria, D. S., Xie, Z., Baek, A., Jiang, J., Elgamal, O. A., Mo, X., Perle, K., Chalmers, J., Schmittgen, T. D., & Phelps, M. A. (2017). Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J Extracell Vesicles, 6(1), 1324730.

    PubMed  PubMed Central  Google Scholar 

  111. Zhang, B., Yeo, R. W. Y., Lai, R. C., Sim, E. W. K., Chin, K. C., & Lim, S. K. (2018). Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway. Cytotherapy, 20(5), 687–696.

    CAS  PubMed  Google Scholar 

  112. Jo, W., Kim, J., Yoon, J., Jeong, D., Cho, S., Jeong, H., Yoon, Y. J., Kim, S. C., Gho, Y. S., & Park, J. (2014). Large-scale generation of cell-derived nanovesicles. Nanoscale, 6(20), 12056–12064.

    ADS  CAS  PubMed  Google Scholar 

  113. Eckert, M. A., Vu, Q., Xie, K., Yu, J., Liao, W., Cramer, S. C., & Zhao, W. (2013). Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. Journal of Cerebral Blood Flow and Metabolism, 33(9), 1322–1334.

    PubMed  PubMed Central  Google Scholar 

  114. Fan, Y., Shen, F., Frenzel, T., Zhu, W., Ye, J., Liu, J., Chen, Y., Su, H., Young, W. L., & Yang, G. Y. (2010). Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Annals of Neurology, 67(4), 488–497.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Zhang, Z. G., Zhang, L., Jiang, Q., & Chopp, M. (2002). Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circulation Research, 90(3), 284–288.

    CAS  PubMed  Google Scholar 

  116. Taguchi, A., Soma, T., Tanaka, H., Kanda, T., Nishimura, H., Yoshikawa, H., Tsukamoto, Y., Iso, H., Fujimori, Y., Stern, D. M., Naritomi, H., & Matsuyama, T. (2004). Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. The Journal of Clinical Investigation, 114(3), 330–338.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Chen, J., Sanberg, P. R., Li, Y., Wang, L., Lu, M., Willing, A. E., Sanchez-Ramos, J., & Chopp, M. (2001). Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke, 32(11), 2682–2688.

    CAS  PubMed  Google Scholar 

  118. Roche, E. T., Hastings, C. L., Lewin, S. A., Shvartsman, D., Brudno, Y., Vasilyev, N. V., O’Brien, F. J., Walsh, C. J., Duffy, G. P., & Mooney, D. J. (2014). Comparison of biomaterial delivery vehicles for improving acute retention of stem cells in the infarcted heart. Biomaterials, 35(25), 6850–6858.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Berra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003). HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO Journal, 22(16), 4082–4090.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Jaakkola, P., Mole, D. R., Tian, Y. M., Wilson, M. I., Gielbert, J., Gaskell, S. J., von Kriegsheim, A., Hebestreit, H. F., Mukherji, M., Schofield, C. J., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292(5516), 468–472.

    ADS  CAS  PubMed  Google Scholar 

  121. Wu, S., Nishiyama, N., Kano, M. R., Morishita, Y., Miyazono, K., Itaka, K., Chung, U. I., & Kataoka, K. (2008). Enhancement of angiogenesis through stabilization of hypoxia-inducible factor-1 by silencing prolyl hydroxylase domain-2 gene. Molecular Therapy, 16(7), 1227–1234.

    CAS  PubMed  Google Scholar 

  122. Wang, C., Lin, G., Luan, Y., Ding, J., Li, P. C., Zhao, Z., Qian, C., Liu, G., Ju, S., & Teng, G. J. (2019). HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke. Biomaterials, 197, 229–243.

    CAS  PubMed  Google Scholar 

  123. 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.

  124. Li, C., Zhao, Z., Luo, Y., Ning, T., Liu, P., Chen, Q., Chu, Y., Guo, Q., Zhang, Y., Zhou, W., Chen, H., Zhou, Z., Wang, Y., Su, B., You, H., Zhang, T., Li, X., Song, H., Li, C., … Jiang, C. (2021). Macrophage-disguised manganese dioxide nanoparticles for neuroprotection by reducing oxidative stress and modulating inflammatory microenvironment in acute ischemic stroke. Adv Sci (Weinh), 8(20), e2101526.

    PubMed  Google Scholar 

  125. Liu, Y., Ai, K., Ji, X., Askhatova, D., Du, R., Lu, L., & Shi, J. (2017). Comprehensive insights into the multi-antioxidative mechanisms of melanin nanoparticles and their application to protect brain from injury in ischemic stroke. Journal of the American Chemical Society, 139(2), 856–862.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Li, X., Han, Z., Wang, T., Ma, C., Li, H., Lei, H., Yang, Y., Wang, Y., Pei, Z., Liu, Z., Cheng, L., & Chen, G. (2022). Cerium oxide nanoparticles with antioxidative neurorestoration for ischemic stroke. Biomaterials, 291, 121904.

    CAS  PubMed  Google Scholar 

  127. Shi, J., Yang, Y., Yin, N., Liu, C., Zhao, Y., Cheng, H., Zhou, T., Zhang, Z., & Zhang, K. (2022). Engineering CXCL12 biomimetic decoy-integrated versatile immunosuppressive nanoparticle for ischemic stroke therapy with management of overactivated brain immune microenvironment. Small Methods, 6(1), e2101158.

    PubMed  Google Scholar 

  128. Tian, T., Cao, L., He, C., Ye, Q., Liang, R., You, W., Zhang, H., Wu, J., Ye, J., Tannous, B. A., & Gao, J. (2021). Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia. Theranostics, 11(13), 6507–6521.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Yang, H., Luo, Y., Hu, H., Yang, S., Li, Y., Jin, H., Chen, S., He, Q., Hong, C., Wu, J., Wan, Y., Li, M., Li, Z., Yang, X., Su, Y., Zhou, Y., & Hu, B. (2021). pH-Sensitive, Cerebral vasculature-targeting hydroxyethyl starch functionalized nanoparticles for improved angiogenesis and neurological function recovery in ischemic stroke. Adv Healthc Mater, 10(12), e2100028.

    PubMed  Google Scholar 

  130. Deng, G., Ma, C., Zhao, H., Zhang, S., Liu, J., Liu, F., Chen, Z., Chen, A. T., Yang, X., Avery, J., Zou, P., Du, F., Lim, K. P., Holden, D., Li, S., Carson, R. E., Huang, Y., Chen, Q., Kimberly, W. T., … Zhou, J. (2019). Anti-edema and antioxidant combination therapy for ischemic stroke via glyburide-loaded betulinic acid nanoparticles. Theranostics, 9(23), 6991–7002.

    CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Neurology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, Jiangsu, China

    Defeng Cao, Wenya Chen, Aijin Ma, Manyun Cheng & Bona Wu

  2. Department of Neurology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, 213017, Jiangsu, China

    Defeng Cao, Wenya Chen, Aijin Ma, Manyun Cheng & Bona Wu

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BW is the corresponding author who contributed to the review conception, design, and revision. DC prepared the manuscript and wrote the major part of the manuscript. WC, AM, and M collected and discussed the literature. BW helped to revise the manuscript. All authors approved the final version of this manuscript.

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Cao, D., Chen, W., Ma, A. et al. Nanoparticles Treat Ischemic Stroke by Responding to Stroke Microenvironment. BioNanoSci. 14, 380–394 (2024). https://doi.org/10.1007/s12668-023-01247-2

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