MRI relaxivity enhancement of gadolinium oxide nanoshells with a controllable shell thickness

Abstract

Gadolinium oxide-based core-shelled nanoparticles have recently emerged as novel magnetic resonance imaging contrast agents for high relaxivity and tumor targeting. However, their relaxivity enhancement mechanism has not yet been clearly understood. We prepared highly dispersible and uniform core-shell structured nanoparticles by encapsulating silica spheres (90 nm in diameter) with gadolinium oxide shells of different thicknesses (from 1.5 nm to 20 nm), and proved experimentally that the shell thickness has an inverse effect on relaxivity. The core-shelled nanoparticles are of a larger relaxivity than the commercial contrast agent Gd-DTPA, with an enhancement from 1.8 to 7.3 times. Based on the Solomon-Bloembergen-Morgan theory which is usually adopted for interpreting the relaxation changes of water protons in Gd3+ chelates, we introduced a shielding ansatz of nanoshells and derived a concise formula specifically to correlate the relaxivity of this sort of core-shelled nanoparticles with the shell thickness directly. The formula calculation is well consistent with the experimental results, and the formula can be generally applied to evaluate the relaxation enhancement underlying the high relaxivity of any core-shelled nanoparticle. Furthermore, the core-shelled nanoparticles possess a negligible nanotoxicity according to the in vitro cytotoxicity and in vivo histopathology and hematology assays. The enhanced signals of in vivo tumor-targeted magnetic resonance imaging indicate that the ultrathin gadolinium oxide nanoshells may function as a potential candidate for advanced positive contrast agents in further clinical applications.

Nanoparticle-Based Paramagnetic Contrast Agents for Magnetic Resonance Imaging

“…A study by Yin et al produced silica nanoparticles coated in a Gd 2 O 3 nanoshell of varying thicknesses. By systematically changing the thickness of the silica shell, the variations in relaxivity values could be investigated and demonstrated that a thinner shell resulted in larger r 1 values [47].…”

Magnetic Nanomaterials as Contrast Agents for MRI

“…Nonetheless, ultrasmall NPs have been found to create aggregates in the cerebrum; as a result, it can be said that the toxicity of the particles is proportional to the maximization of the image potency. Yin et al [ 103 ] developed gadolinium oxide-coated silica nanostructures by exploring different thicknesses of the component. It was demonstrated by varying the thickness of the silica shell over a wide range that with thinner shell values, larger r 1 values can be achieved.…”

Stimulus‐Responsive Nanoparticle Magnetic Resonance Imaging Contrast Agents: Design Considerations and Applications

“…More importantly, because of their structural flexibility, Gd 3+ ‐ and Mn 2+ ‐based nanoparticle systems are more suitable for the design of stimulus‐responsive contrast agents. [ 29,40,45 ]…”