Abstract
This study reports the development of a continuous flow process enabling the synthesis of very small iron oxide nanoparticles (VSION) intended for T1-weighted magnetic resonance imaging (MRI). The influence of parameters, such as the concentration/nature of surfactants, temperature, pressure and the residence time on the thermal decomposition of iron(III) acetylacetonate in organic media was evaluated. As observed by transmission electron microscopy (TEM), the diameter of the resulting nanoparticle remains constant when modifying the residence time. However, significant differences were observed in the magnetic and relaxometric studies. This continuous flow experimental setup allowed the production of VSION with high flow rates (up to 2 mL·min−1), demonstrating the efficacy of such process compared to conventional batch procedure for the scale-up production of VSION.
Highlights
Due to their remarkable superparamagnetic properties and their relatively harmless nature, iron oxide nanoparticles have been at the center of several research in the biomedical field for various applications including magnetic resonance imaging (MRI) [1,2], drug delivery [3,4,5], induced magnetic hyperthermia [6,7] and cell labeling [8,9]
Ntwtaol peaxrpaemriemteernstbalasperdocoenduthreesparerecicsoemsempaornaltyiounsebdetfwoeretnheththeenrumcalelation and the decomposition process: the “heating-up” [33] and the “hot-injection” methods [34]. Both procedures allow the formation of nearly monodisperse iron oxide nanoparticles, with tunable sizes, by varying the experimental parameters based on the precise separation between the nucleation and the
Both procedures allow the formation of nearly monodisperse iron oxide nanoparticles, with tunable sizes, by varying the experimental parameters based on the precise separation between the nucleation and the gNroanwomtahtersitaelsp2s02i0n, 1v0o, xlvFOedR PinEEtRhReEfVoIErWmation mechanism of the nanocrystals [35]
Summary
Due to their remarkable superparamagnetic properties and their relatively harmless nature, iron oxide nanoparticles have been at the center of several research in the biomedical field for various applications including magnetic resonance imaging (MRI) [1,2], drug delivery [3,4,5], induced magnetic hyperthermia [6,7] and cell labeling [8,9]. Concerns about the potential toxicity of gadolinium-based contrast agents have been pointed out for several years with the well-known nephrogenic systemic fibrosis (NSF) [14,15], and more recently, with cases of brain gadolinium deposition in rats [16,17] For these reasons, the development of nanoparticulate T1 contrast agents, based on iron oxide nanoparticles, has become a forward-looking area of research for MRI. Due to a very high surface to volume ratio, flow reactors provide substantial advantages over the conventional batch procedures, very rapid heat transfer enables fast cooling or heating of a solution, as well as precise temperature control [24] These features are interesting for the implementation of the thermal decomposition synthesis of iron oxide nanoparticles. A parametric study is proposed, focusing on the influence of different experimental parameters (concentration and nature of surfactants, temperature, pressure, residence time, and capillary inner diameter) on nanoparticles characteristics, such as the size, the magnetic and relaxometric properties by means of the study of their nuclear magnetic resonance dispersion (NMRD) profiles
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