Magnetic particles are very efficient magnetic resonance imaging (MRI) contrast agents. In recent years, chemists have unleashed their imagination to design multi-functional nanoprobes for biomedical applications including MRI contrast enhancement. This study is focused on the direct relationship between the size and magnetization of the particles and their nuclear magnetic resonance relaxation properties, which condition their efficiency. Experimental relaxation results with maghemite particles exhibiting a wide range of sizes and magnetizations are compared to previously published data and to well-established relaxation theories with a good agreement. This allows deriving the experimental master curve of the transverse relaxivity versus particle size and to predict the MRI contrast efficiency of any type of magnetic nanoparticles. This prediction only requires the knowledge of the size of the particles impermeable to water protons and the saturation magnetization of the corresponding volume. To predict the T(2) relaxation efficiency of magnetic single crystals, the crystal size and magnetization - obtained through a single Langevin fit of a magnetization curve - is the only information needed. For contrast agents made of several magnetic cores assembled into various geometries (dilute fractal aggregates, dense spherical clusters, core-shell micelles, hollow vesicles…), one needs to know a third parameter, namely the intra-aggregate volume fraction occupied by the magnetic materials relatively to the whole (hydrodynamic) sphere. Finally a calculation of the maximum achievable relaxation effect - and the size needed to reach this maximum - is performed for different cases: maghemite single crystals and dense clusters, core-shell particles (oxide layer around a metallic core) and zinc-manganese ferrite crystals.

Nanometric crystals of maghemite are known to exhibit superparamagnetism. Because of the significance of their magnetic moment, maghemite nanoparticles are exceptional contrast agents and are used for magnetic resonance imaging (of the liver, spleen, lymph nodes), for magnetic resonance angiography and for molecular and cellular imaging. The relaxivity of these agents depends on their size, saturation magnetization and magnetic field and also on their degree of clustering. There are different types of maghemite particles whose relaxation characteristics are suited to a specific MRI application. The relaxation induced by maghemite particles is caused by the diffusion of water protons in the inhomogeneous field surrounding the particles. This is well described by a theoretical model that takes magnetite crystal anisotropy and Néel relaxation into account. Another type of superparamagnetic compound is ferritin, the iron-storing protein: it contains a superparamagnetic ferrihydrite core. Even if the resulting magnetic moment of ferritin is far smaller than for magnetite nanoparticles, its massive presence in different organs darkens T(2)-weighted MR images, allowing the noninvasive estimation of iron content, thanks to MRI. The relaxation induced by ferritin in aqueous solutions has been demonstrated to be caused by the exchange of protons between bulk water protons and the surface of the ferrihydrite crystal. However, in vivo, the relaxation properties of ferritin are still unexplained, probably because of protein clustering.

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Understanding the relation between the structure and the reactivity of nanomaterials in the organism is a crucial step towards efficient and safe biomedical applications. The multi-scale approach reported here, allows following the magnetic and structural transformations of multicore maghemite nanoflowers in a medium mimicking intracellular lysosomal environment. By confronting atomic-scale and macroscopic information on the biodegradation of these complex nanostuctures, we can unravel the mechanisms involved in the critical alterations of their hyperthermic power and their Magnetic Resonance imaging T1 and T2 contrast effect. This transformation of multicore nanoparticles with outstanding magnetic properties into poorly magnetic single core clusters highlights the harmful influence of cellular medium on the therapeutic and diagnosis effectiveness of iron oxide-based nanomaterials. As biodegradation occurs through surface reactivity mechanism, we demonstrate that the inert activity of gold nanoshells can be exploited to protect iron oxide nanostructures. Such inorganic nanoshields could be a relevant strategy to modulate the degradability and ultimately the long term fate of nanomaterials in the organism.