Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease

ACS Appl Mater Interfaces. 2019 Nov 6;11(44):41009-41018. doi: 10.1021/acsami.9b12258. Epub 2019 Oct 22.

Abstract

Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.

Keywords: endothelial cell; inflammation; macrophage; molybdenum oxide; photothermal therapy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Atherosclerosis / immunology
  • Atherosclerosis / pathology
  • Atherosclerosis / therapy*
  • Bone Marrow Cells / cytology
  • Carotid Arteries / drug effects
  • Carotid Arteries / pathology
  • Carotid Arteries / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Humans
  • Infrared Rays*
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / radiation effects*
  • Male
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / therapeutic use
  • Metal Nanoparticles / toxicity
  • Mice
  • Mice, Knockout
  • Molybdenum / chemistry
  • Molybdenum / pharmacokinetics
  • Oxides / chemistry
  • Oxides / pharmacokinetics
  • Phagocytosis / radiation effects*
  • Phototherapy
  • Semiconductors
  • Tissue Distribution

Substances

  • Oxides
  • molybdenum dioxide
  • Molybdenum