Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Abstract

Although iron oxide magnetic nanoparticles (MNP) have been proposed for numerous biomedical applications, little is known about their biotransformation and long-term toxicity in the body. Dimercaptosuccinic acid (DMSA)-coated magnetic nanoparticles have been proven efficient for in vivo drug delivery, but these results must nonetheless be sustained by comprehensive studies of long-term distribution, degradation and toxicity. We studied DMSA-coated magnetic nanoparticles effects in vitro on NCTC 1469 nonparenchymal hepatocytes, and analyzed their biodistribution and biotransformation in vivo in C57BL/6 mice. Our results indicate that DMSA-coated magnetic nanoparticles have little effect on cell viability, oxidative stress, cell cycle or apoptosis on NCTC 1469 cells in vitro. In vivo distribution and transformation was studied by alternating current magnetic susceptibility measurements, a technique that permits distinction of MNP from other iron species. Our results show that DMSA-coated MNP accumulate in spleen, liver and lung tissues for extended periods of time, in which nanoparticles undergo a process of conversion from superparamagnetic iron oxide nanoparticles to other nonsuperparamagnetic iron forms, with no significant signs of toxicity.

Sulfhydryl-Modified Fe3O4@SiO2 Core/Shell Nanocomposite: Synthesis and Toxicity Assessment in Vitro

“…Especially, many reports have given prominences to surface functionalization with sulfhydryl by which the chemical properties such as dispersibility, compatibility of Fe 3 O 4 @SiO 2 nanocomposites can be improved dramatically 20-3 22 . The dimercaptosuccinic acid (DMSA) functionalized Fe 3 O 4 attracts considerable attention as a new class of highly dispersible biocompatible material recently [23][24][25] . The Fe 3 O 4 @DMSA nanoparticles are proposed for numerous biomedical applications such as electrochemical sensors, cell labeling and drug delivery due to the special properties of sulfhydryl groups, which makes them preferable in biological applications [23][24][25] .…”

“…The dimercaptosuccinic acid (DMSA) functionalized Fe 3 O 4 attracts considerable attention as a new class of highly dispersible biocompatible material recently [23][24][25] . The Fe 3 O 4 @DMSA nanoparticles are proposed for numerous biomedical applications such as electrochemical sensors, cell labeling and drug delivery due to the special properties of sulfhydryl groups, which makes them preferable in biological applications [23][24][25] . However, there is limited information about a facile synthetic route to prepare Fe 3 O 4 @SiO 2 @DMSA nanoparticles and seldom investigation concerned on their biocompatibility.…”

Long‐Term Stability and Reproducibility of Magnetic Colloids Are Key Issues for Steady Values of Specific Power Absorption over Time

“…[13] Therefore, colloidal stability against agglomeration and precipitation is also an essential requirement for biomedical applications of ferrofluids. [14], [15] It is mostly the surface chemistry that determines the trend of the nanoparticles in the media carrier to aggregate in clusters, due to magnetic attractive forces between the particles and to the Van-der Walls long range attractive forces between particles. [13] The balance between several forms of energy (attractive and repulsive forces) and the thermal energy which determine the stability is influenced by the volume fraction, size distribution and temperature.…”

Magnetic drug delivery systems

“…There is no notable influence on cell proliferation. It was further proved that treatment with various concentrations of DMSA-MNPs led to an insignificant decrease in glutathione (GSH) levels [62]. These results confirm the potential of surface coated MNPs for clinical use.…”