Farooq Muhammad Asim, Johnston Angus P R, Trevaskis Natalie L
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia.
Acta Biomater. 2025 Jan 24;193:65-82. doi: 10.1016/j.actbio.2024.12.039. Epub 2024 Dec 17.
The lymphatic system plays an important role in health and many diseases, such as cancer, autoimmune, cardiovascular, metabolic, hepatic, viral, and other infectious diseases. The lymphatic system is, therefore, an important treatment target site for a range of diseases. Lymph nodes (LNs), rich in T cells, B cells, dendritic cells, and macrophages, are also primary sites of action for vaccines and immunotherapies. Promoting the delivery of therapeutics and vaccines to LNs can, therefore, enhance treatment efficacy and facilitate avoidance of off-target side effects by enabling a reduction in therapeutic dose. Several nanoparticle (NP) based delivery systems, such as polymeric NPs, lipid NPs, liposomes, micelles, and dendrimers, have been reported to enhance the delivery of therapeutics and/or vaccines to LNs. Specific uptake into the lymph following injection into tissues is highly dependent on particle properties, particularly particle size, as small molecules are more likely to be taken up by blood capillaries due to higher blood flow rates, whereas larger molecules and NPs can be specifically transported via the lymphatic vessels to LNs as the initial lymphatic capillaries are more permeable than blood capillaries. Once NPs enter LNs, particle properties also have an important influence on their disposition within the node and association with immune cells, which has significant implications for the design of vaccines and immunotherapies. This review article focuses on the impact of NP properties, such as size, surface charge and modification, and route of administration, on lymphatic uptake, retention, and interactions with immune cells in LNs. We suggest that optimizing all these factors can enhance the efficacy of vaccines or therapeutics with targets in the lymphatics and also be helpful for the rational design of vaccines. STATEMENT OF SIGNIFICANCE: The lymphatic system plays an essential role in health and is an important treatment target site for a range of diseases. Promoting the delivery of immunotherapies and vaccines to immune cells in lymph nodes can enhance efficacy and facilitate avoidance of off-target side effects by enabling a reduction in therapeutic dose. One of the major approaches used to deliver therapeutics and vaccines to lymph nodes is via injection in nanoparticle delivery systems. This review aims to provide an overview of the impact of nanoparticle properties, such as size, surface charge, modification, and route of administration, on lymphatic uptake, lymph node retention, and interactions with immune cells in lymph nodes. This will inform the design of future improved nanoparticle systems for vaccines and immunotherapies.
淋巴系统在健康和许多疾病中发挥着重要作用，如癌症、自身免疫性疾病、心血管疾病、代谢性疾病、肝脏疾病、病毒性疾病及其他感染性疾病。因此，淋巴系统是一系列疾病的重要治疗靶点。富含T细胞、B细胞、树突状细胞和巨噬细胞的淋巴结也是疫苗和免疫疗法的主要作用部位。因此，促进治疗药物和疫苗向淋巴结的递送可以提高治疗效果，并通过降低治疗剂量来避免脱靶副作用。据报道，几种基于纳米颗粒（NP）的递送系统，如聚合物纳米颗粒、脂质纳米颗粒、脂质体、胶束和树枝状大分子，可增强治疗药物和/或疫苗向淋巴结的递送。注射到组织后，纳米颗粒在淋巴管中的特异性摄取高度依赖于颗粒特性，尤其是粒径，因为小分子由于血流速度较高更容易被毛细血管摄取，而大分子和纳米颗粒可以通过淋巴管特异性转运至淋巴结，因为初始淋巴管比毛细血管更具渗透性。一旦纳米颗粒进入淋巴结，颗粒特性对其在淋巴结内的分布以及与免疫细胞的相互作用也有重要影响，这对疫苗和免疫疗法的设计具有重要意义。这篇综述文章重点关注纳米颗粒特性，如大小、表面电荷和修饰以及给药途径，对淋巴结中淋巴摄取、滞留以及与免疫细胞相互作用的影响。我们认为，优化所有这些因素可以提高针对淋巴管靶点的疫苗或治疗药物的疗效，也有助于合理设计疫苗。
淋巴系统在健康中起着至关重要的作用，是一系列疾病的重要治疗靶点。促进免疫疗法和疫苗向淋巴结中的免疫细胞递送可以提高疗效，并通过降低治疗剂量来避免脱靶副作用。将治疗药物和疫苗递送至淋巴结的主要方法之一是通过纳米颗粒递送系统进行注射。本综述旨在概述纳米颗粒特性，如大小、表面电荷、修饰和给药途径，对淋巴摄取、淋巴结滞留以及与淋巴结中免疫细胞相互作用的影响。这将为未来改进的用于疫苗和免疫疗法的纳米颗粒系统的设计提供参考。
