A comprehensive toxicity evaluation of novel amino acid-modified magnetic ferrofluids for magnetic resonance imaging

Amino Acids. 2019 Jun;51(6):929-943. doi: 10.1007/s00726-019-02726-1. Epub 2019 Mar 26.

Abstract

Stem cells have been widely exploited as remedial agents in regenerative medicine due to its tremendous potential in treatment of various debilitating diseases. In spite of this fact, there is need of a reliable, clinically applicable cell tracker for deciphering the homing and distribution of stem cells post-transplantation. Researchers have proposed the use of superparamagnetic magnetite (Fe3O4) nanoparticles for in vivo and in vitro tracking and imaging of stem cells. However, there is not much understanding of the chemical coatings on the nanoparticles, which is very important for the sustainability of stem cells in biological system. For any biomedical applications, the surface properties and the core structure of nanoparticles play a significant role. This study reports surface modification of magnetic Fe3O4 nanofluid with biocompatible amino acids viz., arginine and histidine to maintain colloidal stability at neutral pH, impart least disruption when encountered with the biological system and allow labeling with mesenchymal stem cells (MSCs). The size of amino acids-modified magnetic nanoferrofluid (AA@MNFs) was restricted to 15-25 nm for enhanced uptake in stem cells. In vitro cytotoxicity profile of stem cells labeled AA@MNFs was estimated using various assays like MTT, LDH and AO/EtBr followed by detailed pre-clinical toxicity assessment of AA@MNFs which illustrated least toxicity effects in major tissues of the animals. In vitro MRI scans of the stem cells labeled AA@MNFs confirmed the suitability of the reported ferrofluids for the use as MR contrast agents.

Keywords: Acute toxicity; Amino acid; Ferrofluid; In vitro cytotoxicity; Magnetic resonance imaging; Mesenchymal stem cells.

MeSH terms

  • Animals
  • Arginine / chemistry
  • Biocompatible Materials / chemistry
  • Cell Line
  • Cell Tracking
  • Contrast Media / chemistry*
  • Contrast Media / toxicity*
  • Female
  • Ferric Compounds / chemistry*
  • Histidine / chemistry
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / toxicity
  • Mesenchymal Stem Cells / drug effects*
  • Rats
  • Rats, Wistar
  • Surface Properties

Substances

  • Biocompatible Materials
  • Contrast Media
  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide
  • Histidine
  • Arginine