Schudel Alex, Francis David M, Thomas Susan N
School of Materials Science and Engineering, Georgia institute of Technology, Atlanta, GA, USA.
Parker H. Petit institute for Bioengineering and Bioscience, Georgia institute of Technology, Atlanta, GA, USA.
Nat Rev Mater. 2019 Jun;4(6):415-428. doi: 10.1038/s41578-019-0110-7. Epub 2019 May 2.
A significant fraction of the total immune cells in the body are located in several hundred lymph nodes, in which lymphocyte accumulation, activation and proliferation are organized. Therefore, targeting lymph nodes provides the possibility to directly deliver drugs to lymphocytes and lymph node-resident cells and thus to modify the adaptive immune response. However, owing to the structure and anatomy of lymph nodes, as well as the distinct localization and migration of the different cell types within the lymph node, it is difficult to access specific cell populations by delivering free drugs. Materials can be used as instructive delivery vehicles to achieve accumulation of drugs in the lymph nodes and to target specific lymph node-resident cell subtypes. In this Review, we describe the compartmental architecture of lymph nodes and the cell and fluid transport mechanisms to and from lymph nodes. We discuss the different entry routes into lymph nodes and how they can be explored for drug delivery, including the lymphatics, blood capillaries, high endothelial venules, cell-mediated pathways, homing of circulating lymphocytes and direct lymph node injection. We examine different nanoscale and microscale materials for the targeting of specific immune cells and highlight their potential for the treatment of immune dysfunction and for cancer immunotherapy. Finally, we give an outlook to the field, exploring how lymph node targeting can be improved by the use of materials.
体内相当一部分免疫细胞位于数百个淋巴结中，淋巴细胞的聚集、激活和增殖在这些淋巴结中有序进行。因此，靶向淋巴结为直接将药物递送至淋巴细胞和驻留在淋巴结中的细胞提供了可能性，从而可以调节适应性免疫反应。然而，由于淋巴结的结构和解剖学特征，以及淋巴结内不同细胞类型独特的定位和迁移方式，通过递送游离药物来靶向特定细胞群体具有一定难度。材料可作为指导性递送载体，以实现药物在淋巴结中的蓄积，并靶向特定的驻留在淋巴结中的细胞亚型。在本综述中，我们描述了淋巴结的分区结构以及进出淋巴结的细胞和液体转运机制。我们讨论了进入淋巴结的不同途径，以及如何利用这些途径进行药物递送，包括淋巴管、毛细血管、高内皮微静脉、细胞介导途径、循环淋巴细胞归巢和直接淋巴结注射。我们研究了用于靶向特定免疫细胞的不同纳米级和微米级材料，并强调了它们在治疗免疫功能障碍和癌症免疫治疗方面的潜力。最后，我们对该领域进行了展望，探讨如何通过使用材料来改进淋巴结靶向。
