McCright Jacob, Naiknavare Ritika, Yarmovsky Jenny, Maisel Katharina
Department of Bioengineering, University of Maryland College Park, College Park, MD, United States.
Front Pharmacol. 2022 Jun 3;13:887402. doi: 10.3389/fphar.2022.887402. eCollection 2022.
The lymphatics transport material from peripheral tissues to lymph nodes, where immune responses are formed, before being transported into systemic circulation. With key roles in transport and fluid homeostasis, lymphatic dysregulation is linked to diseases, including lymphedema. Fluid within the interstitium passes into initial lymphatic vessels where a valve system prevents fluid backflow. Additionally, lymphatic endothelial cells produce key chemokines, such as CCL21, that direct the migration of dendritic cells and lymphocytes. As a result, lymphatics are an attractive delivery route for transporting immune modulatory treatments to lymph nodes where immunotherapies are potentiated in addition to being an alternative method of reaching systemic circulation. In this review, we discuss the physiology of lymphatic vessels and mechanisms used in the transport of materials from peripheral tissues to lymph nodes. We then summarize nanomaterial-based strategies to take advantage of lymphatic transport functions for delivering therapeutics to lymph nodes or systemic circulation. We also describe opportunities for targeting lymphatic endothelial cells to modulate transport and immune functions.
淋巴管将物质从外周组织输送到淋巴结，在那里形成免疫反应，然后再进入体循环。淋巴管在运输和液体稳态中起关键作用，淋巴管功能失调与包括淋巴水肿在内的多种疾病相关。间质内的液体进入初始淋巴管，其中的瓣膜系统可防止液体回流。此外，淋巴管内皮细胞会产生关键趋化因子，如CCL21，它可引导树突状细胞和淋巴细胞迁移。因此，淋巴管是一种有吸引力的递送途径，可将免疫调节治疗输送到淋巴结，在那里免疫疗法会得到增强，同时它也是进入体循环的另一种方式。在这篇综述中，我们讨论了淋巴管的生理学以及从外周组织向淋巴结输送物质所采用的机制。然后我们总结了基于纳米材料的策略，以利用淋巴运输功能将治疗药物递送至淋巴结或体循环。我们还描述了靶向淋巴管内皮细胞以调节运输和免疫功能的机会。
