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The enhanced protective effects of salvianic acid A: A functionalized nanoparticles against ischemic stroke through increasing the permeability of the blood-brain barrier

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Abstract

Ischemic stroke is the leading cause of disability and death worldwide. Currently, the only proven treatment for ischemic stroke is restoring the cerebral blood supply. In addition, some of the tissue is damaged during the subsequent reperfusion because of the overproduction of reactive oxygen species (ROS). Furthermore, antioxidant therapies have shown promise in preclinical studies for the treatment of ischemia-reperfusion injury. However, their therapeutic efficacy has been limited because of their low bioavailability in brain. To resolve this issue, we synthesized ROS-responsive, fan-shaped dendrimer nanoparticles (NPs) and conjugated them with a blood-brain barrier (BBB)-targeting peptide, COG1410, and salvianic acid A (SA), which is an effective antioxidant in ischemic stroke. The BBB targeting peptide acts as a ligand of the nanocarrier system and penetrates the BBB through the endocytosis of the ligand receptor. The results showed that T-SA-NPs not only target and accumulate in the infarct area, they also reduce over 2 times of the infarct area and reverse the behavioral deficits in MCAO mice, which illustrates that these NPs have an effective therapeutic effect on the ischemic stroke. In addition, these NPs had no toxicity in any organs of the body. Importantly, the present study provides an alternative strategy for delivering antioxidants to the brain and achieving targeted therapy of ischemic stroke.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 31571020, 31570856 and 21375133), and Beijing Nova Programme Interdisciplinary Cooperation Project (No. Z191100001119002).

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Authors and Affiliations

  1. State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China

    Yaru Li, Xiaojie Zhang, Xueling Guo, Yang Liu & Libo Du

  2. Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China

    Yaru Li, Xueling Guo, Yang Liu & Libo Du

  3. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Captital Medical University, Beijing, 100053, China

    Zhifeng Qi & Wenjuan Shi

  4. Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050051, China

    Xiaopeng Liu

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  1. Yaru Li
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Correspondence to Zhifeng Qi, Yang Liu or Libo Du.

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The enhanced protective effects of salvianic acid A: A functionalized nanoparticles against ischemic stroke through increasing the permeability of the blood-brain barrier

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Li, Y., Zhang, X., Qi, Z. et al. The enhanced protective effects of salvianic acid A: A functionalized nanoparticles against ischemic stroke through increasing the permeability of the blood-brain barrier. Nano Res. 13, 2791–2802 (2020). https://doi.org/10.1007/s12274-020-2930-6

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