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) T 1 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 x Fe 3−x O 4 @Zn x Mn y Fe 3−x−y O 4 (denoted as Zn x F@Zn x Mn y 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 r 1 relaxivity for Zn 0.4 F@ Zn 0.4 Mn 0.2 F 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 T 1 nanoprobe for advanced molecular imaging.

Nanotheranostics for Image-Guided Cancer Treatment

“…Nuclear medicine imaging has the highest sensitivity (pM range) and quantitative property, but suffers from a poor spatial resolution (mm range) [ 170 ]; CT excels at rapid image acquisition and facile three-dimensional (3D) reconstruction, but has limited resolution in soft tissues [ 171 ]; MRI has a high spatial resolution and excellent soft-tissue contrast with the versatility to provide information regarding tissue metabolism and perfusion. However, MRI suffers from lower sensitivity and hence requires a higher contrast agent dose to achieve necessary resolution [ 172 ], although recent advances in nanotheranostics have enhanced the per particle and per metal ion relaxivity [ 173 , 174 ]. It is also challenging to perform whole-body assessment using MRI and US, and therefore it is foreseeable nuclear imaging will remain as the quantitative whole-body approach in the near future.…”

Fluorescently-tagged magnetic protein nanoparticles for high-resolution optical and ultra-high field magnetic resonance dual-modal cerebral angiography

“…23,39 T 1 relaxivity is sum of the inner-sphere water protons which are directly bound to paramagnetic metal ion and the second-sphere water protons which are exchangeable protons. 39,66,67 The enhanced r 1 of c-FeMNPs could be explained based on increased amount of paramagnetic Fe(III) ions on the NPs surface for inner-sphere contributions. 39 Since good accessibility of water to the metal center is critical for r 1 enhancement, the hydrophilic albumin protein shell around FeMNPs enables f-MPNPs to exhibit a higher r 1 than c-FeMNPs, which suggests increased second-sphere contributions near the magnetic center of f-MPNPs.…”

Design of Magnetic Nanoplatforms for Cancer Theranostics

“…Wei et al [ 79 ] reported the synthesis of a zwitterion (ZES) coated ultrasmall SPIONs with a magnetic core diameter of about 3 nm, a hydrophilic shell thickness of about 1 nm, a low r2/r1 value and a long internal circulation time, for high resolution T1 MRI imaging of vessels with a spatial resolution of about 0.2 mm. Miao et al [ 80 ] studied the effect of different doping of the core–shell structure on the T1 imaging performance of ultrasmall SPIONs. The optimized 3.8 nm Zn x Fe 3−x O4@Zn x Mn y Fe 3−x−y O 4 core–shell ultrasmall SPIONs has an r1 relaxation rate of 20.22 mM −1 s −1 , which is 5.2–fold and 6.5–fold larger than that of the undoped ultrasmall SPIONs and the clinically used Gd–DTPA.…”