Superparamagnetic iron oxide nanoparticles (SPIONs) enable enhanced magnetic drug targeting and theranostic applications. This study investigated potential toxic effects of SPIONs developed for drug delivery applications. Gold-modified SPIONs (SPION-Au-Cit) produced via alkaline precipitation were analyzed in terms of their hydrodynamic size, ζ-potential, magnetic susceptibility, and crystal structure. Biocompatibility of SPION-Au-Cit was tested in vitro in human umbilical vascular endothelial cells (HUVECs) and primary human fibroblasts, as well as in vivo, in chick embryos. SPION-Au-Cit had a hydrodynamic diameter of 120 nm and ζ potential of -60 mV at pH 7. In the flow cytometric analyses, SPION-Au-Cit were well tolerated by primary human fibroblasts up to a concentration of 25 µg Fe/mL, but were toxic to HUVECs at and above 10 µg Fe/mL. In contrast, endothelial toxicity was less pronounced in real-time cell analysis and wound-healing assays, although the particles were strongly internalized by HUVECs. The injection of SPION-Au-Cit (45 µg) into chick embryos resulted in progressive hemoglobin oxidation, leading to high fetal toxicity. The magnetic accumulation of SPIONs under flow conditions was investigated in vitro and modeled in silico. Under arterial-like flow conditions in vitro, a strong time-dependent magnetic accumulation of SPION-Au-Cit was observed at a concentration of 2.5 µg Fe/mL. SPION-Au-Cit showed pronounced toxicity in endothelial cells and chick embryos. Although the magnetic properties of SPION-Au-Cit enable their effective accumulation even under flow conditions, their potential biomedical applications would require both precise targeting and careful dose-finding studies to prevent harmful off-target effects.
Genç et al. (Mon,) studied this question.