Heterogeneous Iron Oxide/Dysprosium Oxide Nanoparticles Target Liver for Precise Magnetic Resonance Imaging of Liver Fibrosis

Abstract

Challenges remain in precisely diagnosing the progress of liver fibrosis in a noninvasive way. We here synthesized small (4 nm) heterogeneous iron oxide/dysprosium oxide nanoparticles (IO-DyO NPs) as a contrast agent (CA) for magnetic resonance imaging (MRI) to precisely diagnose liver fibrosis in vivo at both 7.0 and 9.4 T field strength. Our IO-DyO NPs can target the liver and show an increased T 2 relaxivity along with an increase of magnetic field strength. At a ultrahigh magnetic field, IO-DyO NPs can significantly improve spatial/temporal image resolution and signal-to-noise ratio of the liver and precisely distinguish the early and moderate liver fibrosis stages. Our IO-DyO NP-based MRI diagnosis can exactly match biopsy (a gold standard for liver fibrosis diagnosis in the clinic) but avoid the invasiveness of biopsy. Moreover, our IO-DyO NPs show satisfactory biosafety in vitro and in vivo. This work illustrates an advanced T 2 CA used in ultrahigh-field MRI (UHFMRI) for the precise diagnosis of liver fibrosis via a noninvasive means.

Nanoscale Contrast Agents for Magnetic Resonance Imaging: A Review

“…Notably, these nanoscale MOF-based structures with attractive adaptability have shown multipurpose potentials for surface functionalization (both spherical and inner) to be optimized for a variety of biomedical applications. Another challenge has been to increase the specificity of NCAs for the noninvasive diagnosis of diseases . Several studies have focused on the hybridization and surface functionalization of these materials to improve their targeting and specificity for diagnostic applications .…”

“…Several studies have focused on the hybridization and surface functionalization of these materials to improve their targeting and specificity for diagnostic applications . For instance, heterogeneous iron oxide/dysprosium oxide hybrid NPs (∼4 nm) were designed as NCAs with improved specificity and biosafety for diagnosing liver fibrosis ( in vivo ) . These nanoagents exhibited an enhanced T 2 relaxivity and improved magnetic field strength, which could highly augment the spatial/temporal image resolution and signal-to-noise ratio of the liver at ultrahigh magnetic field, thus providing specific detection of liver fibrosis at early/moderate stages …”

“…Another challenge has been to increase the specificity of NCAs for the noninvasive diagnosis of diseases. 121 Several studies have focused on the hybridization and surface functionalization of these materials to improve their targeting and specificity for diagnostic applications. 14 For instance, heterogeneous iron oxide/dysprosium oxide hybrid NPs (∼4 nm) were designed as NCAs with improved specificity and biosafety for diagnosing liver fibrosis (in vivo).…”

“…121 These nanoagents exhibited an enhanced T 2 relaxivity and improved magnetic field strength, which could highly augment the spatial/temporal image resolution and signal-to-noise ratio of the liver at ultrahigh magnetic field, thus providing specific detection of liver fibrosis at early/moderate stages. 121 Nanotoxicological and biocompatibility assessments are vital in the design of NCAs for clinical applications. Notably, Gd(III) illustrated long-term retention in tissues (such as brain and kidney), which may cause nephrogenic systemic fibrosis and produce potentially fatal conditions in patients, thus raising serious safety concerns and restricting their clinical use.…”

Fabrication of magnetic nanoprobes for ultrahigh-field magnetic resonance imaging

“…9f, AFNP-RGD-enhanced UHF-MRI can detect ∼90.2% of the <5 mm metastases. In a follow-up study, Jiang et al engin-eered a 4 nm heterogeneous iron oxide/dysprosium oxide (IO-DyO) nanoprobe for the precise diagnosis of liver fibrosis in vivo at 7.0 T and 9.4 T. 92 IO-DyO NPs-based MRI diagnosis enabled accurate differentiation between early and moderate liver fibrosis stages, which could be completely matched to the biopsy (the gold standard for clinical liver fibrosis diagnosis) and avoided the invasion of biopsy.…”