Ultrasmall inorganic nanoparticles repair damaged meningeal lymphatic vessels to boost Parkinson’s disease therapy

IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Mengxiao Han, Yaobao Han, Zhilin Jiang, Yifan Gao, Guozhi Cao, Hao Zhang, Tingting Wang, Zhen Li
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Abstract

Meningeal lymphatic vessels (MLVs) have been identified to associate with various neurological diseases, such as traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and brain tumors. Damage to MLVs can exacerbate the pathological progression of these diseases and significantly impede therapeutic efficacy. Therefore, targeted repair of the damaged MLVs has emerged as an innovative strategy for treating these central nervous system (CNS) diseases. In this study, we find that inorganic Cu 2− x Se nanoparticles, rather than conventional endogenous vascular endothelial growth factor-C (VEGF-C), can repair the damaged MLVs to restore their structure and functions. These nanoparticles not only promote the growth and development of lymphatic vessels but also enhance the drainage capacity of impaired MLVs, thereby facilitating the transport of immune cells and macromolecules through these vessels. Unlike the conventional repair of damaged MLVs, this is an instance where inorganic nanoparticles have been explored to stimulate the expression of VEGF-C and its receptor VEGFR3, thereby promoting the structural and functional recovery of these vessels. The enhanced drainage function of MLVs mediated by Cu 2− x Se nanoparticles significantly alleviates the symptoms of pre-formed fibrils (PFFs)-induced Parkinson’s disease in mice. Collectively, our findings demonstrate that inorganic nanoparticles can promote the growth and development of meningeal lymphatics like VEGF-C, providing a cost-effective and innovative strategy for repairing damaged MLVs to boost the therapeutic efficacy of CNS diseases.
超小无机纳米颗粒修复受损脑膜淋巴管,促进帕金森病治疗
脑膜淋巴管(mlv)已被确定与各种神经系统疾病有关,如创伤性脑损伤(TBI)、阿尔茨海默病(AD)、帕金森病、多发性硬化症和脑肿瘤。mlv损伤可加剧这些疾病的病理进展,并显著阻碍治疗效果。因此,靶向修复受损的mlv已成为治疗这些中枢神经系统(CNS)疾病的创新策略。在这项研究中,我们发现无机Cu 2−x Se纳米颗粒,而不是传统的内源性血管内皮生长因子- c (VEGF-C),可以修复受损的mlv,恢复其结构和功能。这些纳米颗粒不仅能促进淋巴管的生长和发育,还能增强受损mlv的引流能力,从而促进免疫细胞和大分子通过淋巴管的运输。与传统修复受损mlv的方法不同,这是一个探索无机纳米颗粒刺激VEGF-C及其受体VEGFR3表达的例子,从而促进这些血管的结构和功能恢复。cu2−x Se纳米颗粒介导的mlv引流功能增强可显著缓解PFFs诱导的小鼠帕金森病症状。总之,我们的研究结果表明,无机纳米颗粒可以促进像VEGF-C这样的脑膜淋巴管的生长和发育,为修复受损的mlv提供了一种具有成本效益的创新策略,从而提高了中枢神经系统疾病的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
19.00
自引率
0.90%
发文量
3575
审稿时长
2.5 months
期刊介绍: The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
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