Cu-Doped Extremely Small Iron Oxide Nanoparticles with Large Longitudinal Relaxivity: One-Pot Synthesis and in Vivo Targeted Molecular Imaging

Abstract

Synthesizing iron oxide nanoparticles for positive contrast in magnetic resonance imaging is the most promising approach to bring this nanomaterial back to the clinical field. The success of this approach depends on several aspects: the longitudinal relaxivity values, the complexity of the synthetic protocol, and the reproducibility of the synthesis. Here, we show our latest results on this goal. We have studied the effect of Cu doping on the physicochemical, magnetic, and relaxometric properties of iron oxide nanoparticles designed to provide positive contrast in magnetic resonance imaging. We have used a one-step, 10 min synthesis to produce nanoparticles with excellent colloidal stability. We have synthesized three different Cu-doped iron oxide nanoparticles showing modest to very large longitudinal relaxivity values. Finally, we have demonstrated the in vivo use of these kinds of nanoparticles both in angiography and targeted molecular imaging.

Iron Oxide Nanoparticles: An Alternative for Positive Contrast in Magnetic Resonance Imaging

“…In this case, an increase in the temperature of the reaction turns over the contrast capabilities from T 2 to T 1 with an r 1 = 11.9 mM −1 s −1 at 1.5 T when the reaction is performed at 120 • C [81]. Very recently, Fernandez-Barahona et al increased this value up to 15.7 mM −1 s −1 , doping the iron oxide core with 4% mol of Cu [99].…”

“…Only a few studies use copper or europium as doping metals. In 2019, our group synthesised extremely small citrate-coated iron oxide nanoparticles doped with Cu as a T 1 -weighted contrast agent [99]. After studying several Cu doping amounts, IONPs doped with 4% mol of Cu (Cu4-NPs) were chosen as the best probe.…”

Thrombo-tag, an in vivo formed nanotracer for the detection of thrombi in mice by fast pre-targeted molecular imaging

“…We have used this nanotracer for tumor detection, 8 in vivo neutrophil labeling, 9 and for improved in vivo MRI signal. 10 Bioorthogonal chemistry, on the other hand, allows for the rapid and selective in vivo conjugation of two compounds that have been previously modified with the corresponding complementary groups. This unparalleled selectivity, even in the presence of the complex mixture of the biological milieu (e.g.…”

Microwave-Driven Synthesis of Iron-Oxide Nanoparticles for Molecular Imaging

“…These properties explain the use of IONPs in all major imaging techniques, with examples in OI [37], PAI [38], SPECT [39], PET [30] and MRI [36], and magnetic resonance imaging [35,40,41]. MRI deserves special mention since it is the most commonly used imaging technique with IONPs due to their magnetic properties.…”

“…It is known that a core size around 3 nm permits producing IONPs with a paramagnetic behavior rather than superparamagnetic, rendering IONPs with large effects on T 1 relaxation time. On this aspect, the use of MW synthesis is also critical since it allows for the rapid synthesis of very small NPs [41,45].…”