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

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.