Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species

Sci Transl Med. 2019 Aug 21;11(506):eaaw7736. doi: 10.1126/scitranslmed.aaw7736.

Abstract

Nanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse to large rabbit and porcine atherosclerosis models, with an emphasis on the solutions we implemented to overcome production and evaluation challenges. Specifically, we integrated translational imaging readouts within our workflow to both analyze the nanoimmunotherapeutic's in vivo behavior and assess treatment response in larger animals. We observed our nanoimmunotherapeutic's anti-inflammatory efficacy in mice, as well as rabbits and pigs. Nanoimmunotherapy-mediated reduction of inflammation in the large animal models halted plaque progression, supporting the approach's translatability and potential to acutely treat atherosclerosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology*
  • Atherosclerosis / therapy*
  • Disease Models, Animal
  • Female
  • Imaging, Three-Dimensional*
  • Immunotherapy*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, HDL / toxicity
  • Magnetic Resonance Imaging
  • Male
  • Mice, Inbred C57BL
  • Nanomedicine*
  • Positron-Emission Tomography
  • Rabbits
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use
  • Species Specificity
  • Swine
  • Tissue Distribution

Substances

  • Apolipoproteins E
  • Lipoproteins, HDL
  • Simvastatin