Nanoparticles for Lymph Node-Directed Delivery

Abstract

Lymph nodes are organs that control immune cells and provide a major pathway for primary tumors to metastasize. A nanoparticles-based strategy has several advantages that make it suitable for achieving effective lymphatic delivery. First, the size of nanoparticles can be tailored to meet a size range appropriate for lymphatic migration. In addition, functionalized nanoparticles can target cells of interest for delivery of drugs or imaging probes. Existing lymph node contrast agents map all lymph nodes regardless of metastasis status; however, by using nanoparticles, it is possible to selectively target lymphatic metastases. Moreover, using functionalized nanoparticles, it is possible to specifically deliver anticancer drugs to metastatic lymph nodes. In this review, we introduce the use of nanoparticles for lymphatic mapping, in particular highlighting design considerations for detecting metastatic lymph nodes. Furthermore, we assess trends in lymph node-targeting nanoparticles in clinical practice and suggest future directions for lymph node-targeting nanoparticles.

Keywords: cancer metastasis; cancer therapy; lymphatic delivery; nanoparticles.

Figure 1

Nanoparticles targeting metastatic lymph nodes. (A) LM mapping agent has no targeting ability on metastatic lymph nodes. (B) Functional nanoparticles specifically detect metastatic lymph nodes, enabling minimal lymphadenectomy and metastatic cancer-specific therapeutic drug delivery.

Figure 2

Structure of a lymph node. Lymph nodes, most of which are kidney-shaped sacs, are located between lymphatic vessels. The outer part of the lymph node is called the cortex and contains B cells that produce antibodies. The remainder of the cortex contains T cells that circulate throughout the body and monitor immune responses. Lymph flows in through the afferent lymphatic duct, which is connected to the convex side of the lymph node, and drains through the efferent lymph vessel.