Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Abstract

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM −1 s −1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

Spin-Dependent Phenomena in Semiconductor Micro-and Nanoparticles—From Fundamentals to Applications

“…The maximal transverse relaxivity accounted 7.3 L/(gs). The latter value corresponds to the molar relaxivity of about 200 L/(mMs) [101], which is close to that reported for CAs based on superparamagnetic iron oxide NPs [100].…”

“…The corresponding maximal relaxivity normalized on the number of Si atoms in NPs is about 0.01 L/(mMs) that is smaller than for the standard CAs based on Gd 3+ ions, which is about 4-6 L/(mMs) [99]. Note, the relaxivity of superparamagnetic iron oxide NPs is reported to be up to 10 2 -10 3 L/(mMs) [100]. However, specially designed porous Si NPs with required number of electron spin centers seem to be considered as potential CAs for biomedical application in MRI [96].…”

Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

“…For example, citrate-coated USPIOs have been shown to temporarily increase ROS in rat macrophages though without cytotoxic effects, 38 while cationic USPIOs apparently induced no microhemorrhage or thrombus, no inflammatory processes, and no effect on hepatic or renal enzymes. 26 Specialized coatings have also been used to more precisely label cells in vivo. The nanoparticle coating can itself be conjugated with molecules of interest.…”

Multi-Modal Nano Particle Labeling of Neurons

“…In order to combine LM and MRI, appropriate agents for both imaging modalities first need to be considered based on their signal strength, toxicity, stability and size. Several classes of MRI-compatible contrast agents are available (Geraldes and Laurent, 2009); with iron oxide nanoparticles meeting most of these requirements, namely provide a strong and stable MRI-signature, with little effects on cellular physiology (e.g., Uchiyama et al, 2015; and see review Shen et al, 2017). Consequently, iron oxide nanoparticles are commonly employed in the field.…”