Targeting Microglia for Therapy of Parkinson’s Disease by Using Biomimetic Ultrasmall Nanoparticles,Journal of the American Chemical Society

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Targeting Microglia for Therapy of Parkinson’s Disease by Using Biomimetic Ultrasmall Nanoparticles
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-12-14 , DOI: 10.1021/jacs.0c09390
Hanghang Liu ₁ , Yaobao Han ₁ , Tingting Wang ₁ , Hao Zhang _{1,

2} , Qi Xu ₁ , Jiaxin Yuan ₁ , Zhen Li ₁

Affiliation

Microglia as an important type of innate immune cell in the brain have been considered as an effective therapeutic target for the treatment of central nervous degenerative diseases. Herein, we report cell membrane coated novel biomimetic Cu2-xSe-PVP-Qe nanoparticles (denoted as CSPQ@CM nanoparticles, where PVP is poly(vinylpyrrolidone), Qe is quercetin, and CM is the cell membrane of neuron cells) for effectively targeting and modulating microglia to treat Parkinson's disease (PD). The CSPQ nanoparticles exhibit multienzyme activities and could effectively scavenge the reactive oxygen species and promote the polarization of microglia into the anti-inflammatory M2-like phenotype to relieve neuroinflammation. We reveal that biomimetic CSPQ@CM nanoparticles targeted microglia through the specific interactions between the membrane surface vascular cells adhering to molecule-1 and α4β1 integrin expressed by microglia. They could significantly improve the symptoms of PD mice to result in an excellent therapeutic efficacy, as evidenced by the recovery of their dopamine level in cerebrospinal fluid, tyrosine hydroxylase, and ionized calcium binding adapter protein 1 to normal levels. Our work demonstrates the great potential of these robust biomimetic nanoparticles in the targeted treatment of PD and other central nervous degenerative diseases.

中文翻译：

使用仿生超小纳米颗粒靶向小胶质细胞治疗帕金森病

小胶质细胞作为大脑中一种重要的先天免疫细胞，被认为是治疗中枢神经退行性疾病的有效治疗靶点。在此，我们报告了细胞膜包被的新型仿生 Cu2-xSe-PVP-Qe 纳米粒子（表示为 CSPQ@CM 纳米粒子，其中 PVP 是聚乙烯吡咯烷酮，Qe 是槲皮素，CM 是神经元细胞的细胞膜），用于有效靶向调节小胶质细胞以治疗帕金森病 (PD)。CSPQ 纳米粒子表现出多酶活性，可以有效清除活性氧，促进小胶质细胞极化为抗炎 M2 样表型，以缓解神经炎症。我们揭示了仿生 CSPQ@CM 纳米颗粒通过粘附在分子 1 上的膜表面血管细胞与小胶质细胞表达的 α4β1 整联蛋白之间的特异性相互作用来靶向小胶质细胞。它们可以显着改善 PD 小鼠的症状，从而产生出色的治疗效果，其脑脊液中的多巴胺水平、酪氨酸羟化酶和离子钙结合接头蛋白 1 恢复到正常水平就证明了这一点。我们的工作证明了这些强大的仿生纳米粒子在靶向治疗 PD 和其他中枢神经退行性疾病方面的巨大潜力。脑脊液中的多巴胺水平、酪氨酸羟化酶和离子钙结合衔接蛋白 1 恢复到正常水平就证明了这一点。我们的工作证明了这些强大的仿生纳米粒子在靶向治疗 PD 和其他中枢神经退行性疾病方面的巨大潜力。脑脊液中的多巴胺水平、酪氨酸羟化酶和离子钙结合衔接蛋白 1 恢复到正常水平就证明了这一点。我们的工作证明了这些强大的仿生纳米粒子在靶向治疗 PD 和其他中枢神经退行性疾病方面的巨大潜力。

更新日期：2020-12-14

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