Redox biology of Leishmania and macrophage targeted nanoparticles for therapy

Nanomedicine (Lond). 2017 Jul;12(14):1713-1725. doi: 10.2217/nnm-2017-0049. Epub 2017 Jun 21.

Abstract

Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug. Receptor-mediated targeted nanoparticles can migrate across the cell membrane barriers and release enclosed drug cargo at sites of infection. This review is focusing on Leishmania-macrophage signaling alterations, its association with drug resistance and role of nanoparticles for receptor mediated macrophage targeting.

Keywords: intracellular delivery; leishmaniasis; macrophage targeting; mannose; nanoparticles; oxidative burst; phagolysosomal vesicles; redox biology; scavenger receptors; trypanothione reductase.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Carriers / metabolism*
  • Drug Delivery Systems / methods*
  • Humans
  • Lectins, C-Type / metabolism
  • Leishmania / drug effects*
  • Leishmania / physiology
  • Leishmaniasis / drug therapy*
  • Leishmaniasis / metabolism
  • Macrophages / metabolism
  • Macrophages / parasitology*
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism
  • Nanoparticles / metabolism*
  • Oxidation-Reduction / drug effects
  • Receptors, Cell Surface / metabolism
  • Receptors, Scavenger / metabolism
  • Trypanocidal Agents / administration & dosage*
  • Trypanocidal Agents / pharmacology

Substances

  • Drug Carriers
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, Scavenger
  • Trypanocidal Agents