Accumulation of gold nano-rods in the failing heart of transgenic mice with the cardiac-specific expression of TNF-α

Heart Vessels. 2019 Mar;34(3):538-544. doi: 10.1007/s00380-018-1241-2. Epub 2018 Aug 29.

Abstract

Gold nano-rods, rod-shaped gold nanoparticles, act as contrast agents for in vivo bioimaging, drug delivery vehicles and thermal converters for photothermal therapy. Pro-inflammatory cytokines play critical roles in the development of heart failure. We examined the delivery of GNRs into the failing heart of a transgenic (TG) mouse model of inflammatory cardiomyopathy with the cardiac-specific overexpression of TNF-α. We modified GNRs with polyethylene glycol (PEG) to avoid cytotoxicity and reduce the rapid clearance of nanoparticles from blood. PEG-modified GNRs (4.5 mM as gold atoms, 200 μL) were administered intravenously to TG (n = 7) and wild-type (WT) mice (n = 5). These were killed 24 h later, and the heart, lung, liver, kidney and spleen were excised. A quantitative analysis of gold was performed using inductively coupled plasma mass or optical emission spectrometry. The amount of gold (ng) in the TG heart (3.24 ± 1.56 ng/mg heart weight) was significantly greater than that in the WT heart (1.01 ± 0.19; p < 0.05). No significant differences were observed among the other organs of TG and WT mice. The amount of gold in the TG heart was significantly and positively correlated with the ratio of the ventricular weight to body weight, which is known to be an index of ventricular hypertrophy. In conclusion, PEG-modified GNRs accumulated in the inflammatory TG heart in proportion with the severity of ventricular hypertrophy.

Keywords: Gold nano-rod; Heart failure; Inflammation; TNF-α.

MeSH terms

  • Animals
  • DNA / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Gold / analysis*
  • Heart Failure / genetics
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Heart Ventricles / chemistry
  • Heart Ventricles / pathology
  • Male
  • Metal Nanoparticles / analysis*
  • Mice
  • Mice, Transgenic
  • Myocardium / chemistry*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Tumor Necrosis Factor-alpha
  • Gold
  • DNA