Gram-Scale Preparation of Iron Oxide Nanoparticles with Renal Clearance Properties for Enhanced T₁-Weighted Magnetic Resonance Imaging

Abstract

Extremely small-sized iron oxide nanoparticles (ESIONs) have been accepted as a potential alternative to gadolinium-based contrast agents for enhanced T 1 -weighted MR imaging. Recently developed zwitterion-coated ESIONs showed a high T 1 contrast power and efficient renal clearing ability, but the tedious preparation steps that required high-cost, unfriendly experimental conditions and a sophisticated phase transition process would likely hinder their clinical translation. Herein, we present a one-pot gram-scale synthesis of zwitterion-capped ultrasmall iron oxide nanoparticles (ZUIONs). The nanoparticles have a core size as small as 3.7 nm and display high colloidal stability in various buffers. The r 1 relaxivity of 2.4 mM −1 s −1 and r 2 /r 1 ratio as low as 2.2 at 1.0 T guarantee their application as effective T 1 MRI contrast agents. In vivo studies showed that ZUIONs could induce a significant contrast enhancement in blood pool and be eliminated from the body mainly through the renal excretion pathway. The combined advantageous features including facile preparation, excellent biocompatibility, strong T 1 MRI contrast effect, appropriate circulation time, and renal clearable property would render ZUIONs attractive for practical applications.

Synthesis and modification of uniform PEG-neridronate-modified magnetic nanoparticles determines prolonged blood circulation and biodistribution in a mouse preclinical model

“…Magnetic nanomaterials, which incorporate metallic, bimetallic, and metal oxide nanoparticles 6 , in particular, maghemite (γ-Fe 2 O 3 ) and magnetite (Fe 3 O 4 ), are advantageous due to their low toxicity 7 , biocompatibility and the possibility of easily modifying the surface with polymer shells, drugs and/or targeting and imaging ligands 8,9 . In organism, intravenously administrated iron oxide nanoparticles are recognized by mononuclear phagocytic system depending on the size and transported to organs, predominantly liver and spleen (d > 8 nm), or filtered via kidneys (d < 8 nm) 10 . Borderline in size excluded by kidneys is not sharp; even 10 or 14 nm particles were found in urine 11,12 .…”

Progress in magnetic Fe3O4nanomaterials in magnetic resonance imaging

“…Hao et al [68] applied zwitterion to improve the preparation method. The improved preparation has two innovations: (1) preparing amphiphilic dopamine sulfonate (ZDS) as the outer layer to improve the application of dopamine; and (2) using diethylene glycol as solution and adopting two-step method to obtain Fe 3 O 4 NPs coated with ZDS (ZUIONs).…”

A pH‐Sensitive Zwitterionic Iron Complex Probe with High Biocompatibility for Tumor‐Specific Magnetic Resonance Imaging

“…We synthesized an iron complex by utilizing a zwitterionic dopamine sulfonate (ZDS) as the chelating ligand, and applied it for tumor imaging (Scheme ). ZDS complexes strongly with Fe 3+ , and we have previously used it to synthesize highly biocompatible iron oxide nanoparticles on a large scale . ZDS is also characterized by electrical neutralization and the ability to interact strongly with water molecules, eliminating the problems of osmolality and nonspecific interaction with serum proteins.…”

“…ZDS complexess trongly with Fe 3 + , [30] and we have previously used it to synthesize highly biocompatible iron oxide nanoparticles on al arge scale. [31] ZDS is also characterized by electrical neutralization and the ability to interact strongly with water molecules, eliminating the problems of osmolality and nonspecific interaction with serum proteins. The resultingc omplex, Fe-ZDS, is the first iron complex-based MRI contrast agent with clear zwitterionic naturer eported to date, and it features excellent biocompatibility and acceptablel evels of renal elimination from the body.Both in vitro and in vivo experiments showed that Fe-ZDS exhibited pH-sensitive T 1 relaxivity and can respond rapidly to the pH environmento ft umor tissues,w hich highlighted its potential as an advanced T 1 contrast agentfor tumor diagnosis.…”