Physiological models for in vivo imaging and targeting the lymphatic system: Nanoparticles and extracellular vesicles

Adv Drug Deliv Rev. 2021 Aug:175:113833. doi: 10.1016/j.addr.2021.113833. Epub 2021 Jun 18.

Abstract

Imaging of the lymphatic vasculature has gained great attention in various fields, not only because lymphatic vessels act as a key draining system in the body, but also for their implication in autoimmune diseases, organ transplant, inflammation and cancer. Thus, neolymphangiogenesis, or the generation of new lymphatics, is typically an early event in the development of multiple tumor types, particularly in aggressive ones such as malignant melanoma. Still, the understanding of how lymphatic endothelial cells get activated at distal (pre)metastatic niches and their impact on therapy is still unclear. Addressing these questions is of particular interest in the case of immune modulators, because endothelial cells may favor or halt inflammatory processes depending on the cellular context. Therefore, there is great interest in visualizing the lymphatic vasculature in vivo. Here, we review imaging tools and mouse models used to analyze the lymphatic vasculature during tumor progression. We also discuss therapeutic approaches based on nanomedicines to target the lymphatic system and the potential use of extracellular vesicles to track and target sentinel lymph nodes. Finally, we summarize main pre-clinical models developed to visualize the lymphatic vasculature in vivo, discussing their applications with a particular focus in metastatic melanoma.

Keywords: Extracellular vesicles; Imaging; Lymph nodes; Lymphangiogenesis; Nanomedicines; Probes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / pathology
  • Humans
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Lymphatic System / diagnostic imaging*
  • Lymphatic System / drug effects
  • Lymphatic System / pathology
  • Lymphatic Vessels / diagnostic imaging
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / pathology
  • Nanoparticle Drug Delivery System*
  • Sentinel Lymph Node / diagnostic imaging
  • Sentinel Lymph Node / pathology

Substances

  • Nanoparticle Drug Delivery System