Summary: | Considerable efforts have been focused on the exploitation of macromolecule ligands for synthesis of magnetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles as <i>T</i><sub>1</sub> 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 Fe<sub>3</sub>O<sub>4</sub> nanoparticles through coprecipitation reaction. The obtained Fe<sub>3</sub>O<sub>4</sub>-PAA, Fe<sub>3</sub>O<sub>4</sub>-PAH, and Fe<sub>3</sub>O<sub>4</sub>-PVA nanoparticles showed <i>T</i><sub>1</sub> contrast performance with <i>r</i><sub>1</sub> relaxivities of 23.4, 60.3, and 30.6 mM s<sup>−1</sup> at 0.5 T (25 °C), and a <i>r</i><sub>2</sub>/<i>r</i><sub>1</sub> ratio of 2.62, 3.82, and 7.26, respectively. The cell viability assay revealed that Fe<sub>3</sub>O<sub>4</sub>-PAA and Fe<sub>3</sub>O<sub>4</sub>-PVA exhibited good biocompatibility, while Fe<sub>3</sub>O<sub>4</sub>-PAH displayed high cytotoxicity. In vivo <i>T</i><sub>1</sub>-weighted (1 T) mice showed that both Fe<sub>3</sub>O<sub>4</sub>-PAA and Fe<sub>3</sub>O<sub>4</sub>-PVA were able to display remarkably brighten the contrast enhancement for the mice tumor and kidney sites, but Fe<sub>3</sub>O<sub>4</sub>-PAA had better contrast performance. This work highlights that the macromolecule ligands play an important role in the biocompatibility and <i>T</i><sub>1</sub> contrast performance of magnetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles.
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