19,20 SPIOs have been widely examined for toxicological effects both in vitro and in vivo.
21–23 Mn-IONPs may exhibit totally different cytotoxicity, however, because Mn
2+-doping changes the crystal structure and increases the number of structural defects that disrupt the well structured electronic configuration of SPIO NPs.
18 Conceptually, the latent potential of Mn
2+ release allows the possibility of metal ion interaction with the intracellular components, which may result in the adverse effects on cell survival.
24,25 Thus, the biological effects of Mn-IONPs need to be specifically investigated. Until recently, researchers have examined the biocompatibility of Mn-IONPs and consistently found that they show a dose- and time-dependent cytotoxicity.