Abstract

Considerable efforts have been focused on the exploitation of macromolecule ligands for synthesis of magnetic Fe3O4 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents, but studies that concern macromolecule ligands with different charges and coordination groups are still limited. Herein, we used poly(acrylic acid) (PAA), poly(allylamine hydrochloride) (PAH), and polyvinyl alcohol (PVA), which possess negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups respectively, as templates and stabilizers to fabricate Fe3O4 nanoparticles through coprecipitation reaction. The obtained Fe3O4-PAA, Fe3O4-PAH, and Fe3O4-PVA nanoparticles showed T1 contrast performance with r1 relaxivities of 23.4, 60.3, and 30.6 mM s−1 at 0.5 T (25 °C), and a r2/r1 ratio of 2.62, 3.82, and 7.26, respectively. The cell viability assay revealed that Fe3O4-PAA and Fe3O4-PVA exhibited good biocompatibility, while Fe3O4-PAH displayed high cytotoxicity. In vivo T1-weighted (1 T) mice showed that both Fe3O4-PAA and Fe3O4-PVA were able to display remarkably brighten the contrast enhancement for the mice tumor and kidney sites, but Fe3O4-PAA had better contrast performance. This work highlights that the macromolecule ligands play an important role in the biocompatibility and T1 contrast performance of magnetic Fe3O4 nanoparticles.

Highlights

  • In the past decade, the utilization of magnetic iron oxide (Fe3O4) nanoparticles as a T1-weighted contrast for magnetic resonance imaging (MRI) has received tremendous attention [1,2,3,4,5,6]

  • The Gd-chelates have great potential accumulative toxicity caused by the leaching out of the Gd ions from the chelate ligand [13], while the Fe3O4 nanoparticles can be degraded in the body and the released iron ions can be subsequently incorporated into iron pools and metabolic processes [10]

  • Giving that poly(acrylic acid) (PAA), poly(allylamine hydrochloride) (PAH), and polyvinyl alcohol (PVA) possess negative, positive and neutral charges with carboxylic acid, amino and hydroxyl coordination groups respectively, we used them as templates and stabilizers to fabricate Fe3O4 nanoparticles through the coprecipitation reaction [49]

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Summary

Introduction

The utilization of magnetic iron oxide (Fe3O4) nanoparticles as a T1-weighted contrast for magnetic resonance imaging (MRI) has received tremendous attention [1,2,3,4,5,6]. The charges of macromolecule ligands are an important parameter for controlling the size and preventing the aggregation of the Fe3O4 nanoparticles, since they usually correspond to the coordination affinity between the coordination groups and metal ions, and the electrostatic interaction between adjacent nanoparticles. We used three macromolecule ligands that possessed negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups, respectively, as templates and stabilizers for the coprecipitation synthesis of small magnetic Fe3O4 nanoparticles (Scheme 1), which showed differences in size, water-dispersibility, cytotoxicity and T1-weight contrast performance. We used three macromolecule ligands that possessed negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups, respectively, as templates and stabilizers for the coprecipitation synthesis of small mNaangomnaetteircialsF2e031O9,49n, 6a9n9oparticles (Scheme 1), which showed differences in size, water-dispersib3iloifty, cytotoxicity and T1-weight contrast performance. Schematic illustration of the coprecipitation synthesis of Fe3O4-poly(acrylic acid) (PAA), Fe3O4-poly(allylamine hydrochloride) (PAH), and Fe3O4-polyvinyl alcohol (PVA) with negative, positive and neutral charges, respectively, as the T1-weight contrast agent

Materials and Methods
In Vitro Cytotoxicity Assay
In Vivo Magnetic Resonance Imaging
Synthesis and Characterization

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