Structure-Relaxivity Mechanism of an Ultrasmall Ferrite Nanoparticle T1 MR Contrast Agent: The Impact of Dopants Controlled Crystalline Core and Surface Disordered Shell.

Abstract

Ultrasmall ferrite nanoparticles (UFNPs) have emerged as powerful magnetic resonance imaging (MRI) T1 nanoprobe for noninvasive visualization of biological events. However, the structure-relaxivity relationship and regulatory mechanism of UFNPs remain elusive. Herein, we developed chemically engineered 3.8 nm ZnxFe3-xO4@ZnxMnyFe3-x-yO4 (denoted as ZnxF@ZnxMnyF) nanoparticles with precise dopants control in both crystalline core and disordered shell as a model system to assess the impact of dopants on the relaxometric properties of UFNPs. It is determined that the core-shell dopant architecture allows the optimal tuning of r1 relaxivity for Zn0.4F@Zn0.4Mn0.2F up to 20.22 mM-1 s-1, which is 5.2-fold and 6.5-fold larger than that of the original UFNPs and the clinically used Gd-DTPA. Moreover, the high-performing UFNPs nanoprobe, when conjugated with a targeting moiety AMD3100, enables the in vivo MRI detection of small lung metastasis with greatly enhanced sensitivity. Our results pave the way toward the chemical design of ultrasensitive T1 nanoprobe for advanced molecular imaging.