颈部和脑膜淋巴管网是纳米粒子逆行运输到大脑的通道

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S477159
Héctor M Ramos-Zaldívar, Iva Polakovicova, Edison Salas-Huenuleo, Claudia P Yefi, David Silva-Ancahuail, Pedro Jara-Guajardo, Juan Esteban Oyarzún, Álvaro Neira-Troncoso, Patricia V Burgos, Viviana A Cavieres, Eloísa Arias-Muñoz, Carlos Martínez, Ana L Riveros, Alejandro H Corvalán, Marcelo J Kogan, Marcelo E Andia
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引用次数: 0

摘要

导言脑膜淋巴管被描述为一条将脑脊液和间质单向输送到颈深淋巴结的通道。然而,这些血管表现出典型的初始淋巴管的解剖和分子特征,周围没有平滑肌,瓣膜很少或没有。鉴于其结构,理论上这种网络可以实现双向运动。尽管如此,我们尚未将其作为纳米粒子从外周组织进入大脑的潜在途径进行评估:方法:我们采用了超顺磁性氧化铁纳米颗粒(SPIONs)、装载有 SPIONs、金纳米棒和中国墨水纳米颗粒的外泌体。SPIONs是通过化学共沉淀法制备的,而外泌体则是通过Exo-Spin柱方案从B16F10黑色素瘤细胞系中分离出来的,并通过电穿孔载入SPIONs。金纳米棒由聚乙二醇功能化。我们利用 C57BL/6 小鼠进行尸检和体内操作。为了评估逆行定向流动,我们将每种纳米粒子溶液注入深颈部淋巴结。头颈部固定后进行磁共振成像和组织学分析:结果:我们在此表明,从 B16F10 黑色素瘤细胞系提取的细胞外囊泡以及超顺磁性氧化铁纳米粒子、金纳米棒和中国墨水纳米粒子在死后和体内颈深淋巴结内给药后,可以完全通过淋巴结构到达 C57BL/6 小鼠的脑膜淋巴管和大脑:讨论:硬脑膜淋巴管的功能解剖在小鼠和人类之间是一致的,这表明我们的研究结果可能对推进使用纳米颗粒的靶向给药系统具有重要意义。了解纳米粒子通过脑膜淋巴管网的逆向运输可能会为纳米医学带来新的治疗方法,为生理和神经病理学背景下的流体动力学提供新的见解。对这一途径的进一步研究可能会为治疗神经系统疾病或加强向大脑的药物输送提供新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain.

Introduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain.

Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis.

Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures.

Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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