L-ferritin: A theranostic agent of natural origin for MRI visualization and treatment of breast cancer

J Control Release. 2020 Mar 10:319:300-310. doi: 10.1016/j.jconrel.2019.12.051. Epub 2019 Dec 31.

Abstract

The altered regulation of iron uptake and metabolism in cancerous cells, along with the potential of this metal to cause oxidative stress and cell death, makes iron overload an attractive therapeutic strategy for cancer treatment. In this study, the selective uptake of native HoS-ferritin (Horse-Spleen Ferritin) was assessed in TS/A breast cancer cells and compared with benign cystadenoma NMuMG. The higher expression of L-ferritin receptor SCARA5 led to an enhanced uptake in TS/A that is detected by the generation of a negative contrast in the corresponding MR images. The toxicity of HoS-ferritin toward TS/A cells has been investigated in detail in vitro, showing that cellular vitality is inversely related to the amount of internalized iron content. Finally, biodistribution and therapeutic efficacy of HoS-ferritin have been shown for the first time in vivo on a orthotopic breast cancer mice model, suggesting that iron overdose delivered by the HoS-ferritin can trigger selective mechanisms of regulated cell death.

Keywords: Ferritin; Iron overloading; Magnetic resonance imaging; Molecular imaging; Theranostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoferritins*
  • Breast Neoplasms* / diagnostic imaging
  • Breast Neoplasms* / drug therapy
  • Female
  • Horses
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Precision Medicine
  • Scavenger Receptors, Class A / metabolism
  • Tissue Distribution

Substances

  • SCARA5 protein, human
  • SCARA5 protein, mouse
  • Scavenger Receptors, Class A
  • Apoferritins