Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Abstract

Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN‐targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future‐oriented discussion, offering critical insights into the field.

Multifunctional Nanoparticle-Loaded Injectable Alginate Hydrogels with Deep Tumor Penetration for Enhanced Chemo-Immunotherapy of Cancer

“…Nanoparticles can act as delivery carriers to deliver immunotherapy drugs to lymph nodes and improve their efficacy in the meantime. On the one hand, nanoparticles with a size of 5–200 nm can enter lymphatic vessels and target lymph nodes through passive drainage . On the other hand, mature DCs that uptake nanoparticles would be home to the lymph nodes, where they present antigens, promote T cell activation, and further proliferation and differentiation, thus activating the antitumor immune response .…”

“…On the one hand, nanoparticles with a size of 5−200 nm can enter lymphatic vessels and target lymph nodes through passive drainage. 36 On the other hand, mature DCs that uptake nanoparticles would be home to the lymph nodes, where they present antigens, promote T cell activation, and further proliferation and differentiation, thus activating the antitumor immune response. 5 To study the retention of IP-NPs@ALG-DH at the injection site and the migration to the lymph node, we synthesized indocyanine green (ICG)-labeled PCL−PEG- tumor cells, and the TAAs produced were quickly captured by IP-NPs-ICG and taken by DCs.…”

Current Progress in the Science of Novel Adjuvant Nano-Vaccine-Induced Protective Immune Responses

“…These nanoparticles can be ingested by APCs, which can stimulate the immunological responses [ 16 ]. According to one theory, NPs can stimulate the development of a cellular immune response by interacting with CD8 + dendritic cells [ 39 ]. A characteristic of NPs is that they can transfer from the subcutaneous tissues to the lymph nodes when they are less than 100 nm in size [ 39 ].…”

“…According to one theory, NPs can stimulate the development of a cellular immune response by interacting with CD8 + dendritic cells [ 39 ]. A characteristic of NPs is that they can transfer from the subcutaneous tissues to the lymph nodes when they are less than 100 nm in size [ 39 ]. A stimulated innate immune response will result from the antigen being delivered to mature immune cells in these nodes [ 39 ].…”

“…A characteristic of NPs is that they can transfer from the subcutaneous tissues to the lymph nodes when they are less than 100 nm in size [ 39 ]. A stimulated innate immune response will result from the antigen being delivered to mature immune cells in these nodes [ 39 ]. According to the study, the use of NPs in a vaccine can increase the antibody production [ 40 ].…”