Lipid nanoparticle formulations for targeting leukocytes with therapeutic RNA in liver fibrosis

Adv Drug Deliv Rev. 2021 Jun:173:70-88. doi: 10.1016/j.addr.2021.03.009. Epub 2021 Mar 25.

Abstract

Obesity and low-grade inflammation are promoters of a multitude of diseases including liver fibrosis. Activation of the mobile leukocytes has a major impact on the outcome of inflammatory disease and can hence foster or mitigate liver fibrosis. This renders immunological targets valuable for directed interventions using nanomedicines. Particularly, RNA-based drugs formulated as lipid nanoparticles (LNP) can open new avenues for the personalized treatment of liver fibrosis both through specific interference and via the induction of the expression of functional and therapeutic proteins. Using microfluidics technology, all components, including lipid-anchored targeting ligands, are assembled in a single-step mixing process. A highlight is set to immunologically relevant liver cell types that are most vulnerable for being reached by LNP. A selection of LNP from other therapeutic fields applicable for reaching these cells in liver fbrosis is summarized. Furthermore, recent proceedings and major obstacles in the field of these targeted LNP are presented.

Keywords: Immune cells; Immunology; Immunotherapy; Lipid nanoparticles; Liver fiibrosis; Macrophages; Microfluidic mixing; Monocytes; Nanomedicines; Nanotechnology; Nucleic acid therapeutics; Obesity; Reticuloendothelial cells; T cells.

Publication types

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

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Humans
  • Leukocytes / drug effects*
  • Leukocytes / immunology
  • Lipids / chemistry*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / immunology
  • Nanoparticles / chemistry*
  • RNA / pharmacology*

Substances

  • Lipids
  • RNA