Interactions of Nanoparticles with Macrophages and Feasibility of Drug Delivery for Asthma

Int J Mol Sci. 2022 Jan 30;23(3):1622. doi: 10.3390/ijms23031622.

Abstract

Understanding the interaction between nanoparticles and immune cells is essential for the evaluation of nanotoxicity and development of nanomedicines. However, to date, there is little data on the membrane microstructure and biochemical changes in nanoparticle-loaded immune cells. In this study, we observed the microstructure of nanoparticle-loaded macrophages and changes in lipid droplets using holotomography analysis. Quantitatively analyzing the refractive index distribution of nanoparticle-loaded macrophages, we identified the interactions between nanoparticles and macrophages. The results showed that, when nanoparticles were phagocytized by macrophages, the number of lipid droplets and cell volume increased. The volume and mass of the lipid droplets slightly increased, owing to the absorption of nanoparticles. Meanwhile, the number of lipid droplets increased more conspicuously than the other factors. Furthermore, alveolar macrophages are involved in the development and progression of asthma. Studies have shown that macrophages play an essential role in the maintenance of asthma-related inflammation and tissue damage, suggesting that macrophage cells may be applied to asthma target delivery strategies. Therefore, we investigated the target delivery efficiency of gold nanoparticle-loaded macrophages at the biodistribution level, using an ovalbumin-induced asthma mouse model. Normal and severe asthma models were selected to determine the difference in the level of inflammation in the lung. Consequently, macrophages had increased mobility in models of severe asthma, compared to those of normal asthma disease. In this regard, the detection of observable differences in nanoparticle-loaded macrophages may be of primary interest, as an essential endpoint analysis for investigating nanomedical applications and immunotheragnostic strategies.

Keywords: 3D holotomography; asthma; drug delivery; lipid droplet; macrophages; nanoparticles.

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / diagnostic imaging*
  • Asthma / metabolism
  • Disease Models, Animal
  • Drug Delivery Systems
  • Feasibility Studies
  • Female
  • Gold / pharmacokinetics*
  • Lipopolysaccharides / adverse effects*
  • Lung / chemistry*
  • Lung / diagnostic imaging
  • Macrophages / chemistry
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / transplantation*
  • Metal Nanoparticles
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Ovalbumin / adverse effects*
  • RAW 264.7 Cells
  • Tissue Distribution
  • Tomography

Substances

  • Lipopolysaccharides
  • Nitric Oxide
  • Gold
  • Ovalbumin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse