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 Zn_<i>x</i>Fe_3-<i>x</i>O₄@Zn_<i>x</i>Mn_<i>y</i>Fe_{3-<i>x</i>-<i>y</i>}O₄ (denoted as Zn_<i>x</i>F@Zn_<i>x</i>Mn_<i>y</i>F) 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 Zn_0.4F@Zn_0.4Mn_0.2F 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 <i>in vivo</i> 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.