Nanomaterial-Based Drug Delivery System Targeting Lymph Nodes

Abstract

The lymphatic system plays an indispensable role in humoral balance, lipid metabolism, and immune regulation. The lymph nodes (LNs) are known as the primary sites of tumor metastasis and the metastatic LNs largely affected the prognosis of the patiens. A well-designed lymphatic-targeted system favors disease treatment as well as vaccination efficacy. In recent years, development of nanotechnologies and emerging biomaterials have gained increasing attention in developing lymph-node-targeted drug-delivery systems. By mimicking the endogenous macromolecules or lipid conjugates, lymph-node-targeted nanocarries hold potential for disease diagnosis and tumor therapy. This review gives an introduction to the physiological functions of LNs and the roles of LNs in diseases, followed by a review of typical lymph-node-targeted nanomaterial-based drug-delivery systems (e.g., liposomes, micelles, inorganic nanomaterials, hydrogel, and nanocapsules). Future perspectives and conclusions concerned with lymph-node-targeted drug-delivery systems are also provided.

Keywords: cancer; drug-delivery system; immunology; lymph node; targeted therapy.

Figure 1

A brief illustration of the human lymphatic system.

Figure 2

A brief schematic of lymph node anatomy and the locations of lymphocytes.

Figure 3

Schematic illustration of LNs targeted nano-drug-delivery system for various cancer therapy. (A) Typical LN-targeted nano-DDS, including liposomes, micelles, inorganic nanomaterials, hydrogel, and nanocapsules, which are loaded with therapeutics or adjuvants for targeted delivery to draining LNs. (B) Possible echanisms of nanoparticle endosomal escape, including membrane destabilization, osmotic rupture, and nano-cargo release with particle swelling. (C) After injection, DDS is efficiently drained to lymph nodes, uptake by DCs, maturating DCs, and presenting peptide-MHC I/MHC II complexes to CD8⁺/CD4⁺ T cells, respectively, activating CD4⁺ T cells and CD8⁺ T cells, thereby, eliciting robust and durable anti-tumor immunity. The targeting strategies are widely applied in the treatment of malignant tumors, such as melanoma, colorectal cancer, liver cancer, pancreatic cancer, lung cancer, and cervical cancer.

Figure 4

Schematic representation of functional inorganic nanoparticle-based drug-delivery systems targeting LNs. (A) Transmission electron microscope (TEM) images of modified AuNPs. Reproduced from Suresh Kumar Gulla et al. [122], which is licensed under the Creative Commons License. (B) Schematic drawings of the preparation of magnetic multiwalled carbon nanotubes (mMWNTs) and the magnetic LN-targeted chemotherapy in a murine model. Reproduced from Feng Yang et al. [225], which is licensed under Elsevier. (C) A brief illustration of the interaction of double-receptor-targeting IONPs conjugated with LHRH and AE105 peptides with a cancer cell. Reproduced from Md shakir Uddin ahmed et al. [128], which is licensed under the Creative Commons Attribution—Non Commercial (unported, v3.0) License. (D) Schematic drawings of GDMON -P+OVA+CpG enhanced cancer immunotherapy. Functionalized GDMON can transport antigenic proteins OVA and TLR9 agonists to APCs and induce endosome escape. Reproduced from Yao Lu et al. [220], which is licensed under Copyright © 2022 Elsevier B.V.