Tumor-Targeting T ₁ MRI Contrast Agents with Antioxidant Effects: Gadolinium Oxide Nanoparticles Grafted with Polydopamine- and Polyserotonin-Conjugated Polyacrylic Acids

Polydopamine (pdop) and polyserotonin (pser) can target tumor cells through their conjugation with dopamine (dop)- and serotonin (ser)-receptors overexpressed on tumor cells. In this study, pdop- or pser-conjugated poly-(acrylic acid) (PAA)-grafted gadolinium oxide nanoparticles (denoted as pdop-PAA-Gd₂O₃ and pser-PAA-Gd₂O₃ NPs) were synthesized for the first time via polymerization of dop and ser during their conjugation with the PAA component of PAA-Gd₂O₃ NPs; then, the obtained pdop-PAA-Gd₂O₃ and pser-PAA-Gd₂O₃ NPs were applied as tumor-targeting positive (T₁) magnetic resonance imaging (MRI) contrast agents. In addition, their antioxidant effects were investigated by evaluating their ability to suppress the rhodamine B (Rh B) oxidation reaction induced by reactive oxygen species (ROS) in aqueous solution. The core Gd₂O₃ NPs had average particle diameters of ∼2 nm. The pdop-PAA-Gd₂O₃ and pser-PAA-Gd₂O₃ NPs showed high longitudinal water proton spin relaxivity (<i>r</i> ₁) values (28.6-35.4 s^-1 mM^-1; <i>r</i> ₂/<i>r</i> ₁ ratios <2.5), which were 8-10 times higher than those of commercial T₁ MRI contrast agents based on Gd-chelates. In addition, they exhibited higher T₁ contrast enhancements at tumor sites compared with PAA-Gd₂O₃ NPs used as control, along with clear antioxidant effects to scavenge ROS in solution reactions. The results of this study indicate that pdop-PAA-Gd₂O₃ and pser-PAA-Gd₂O₃ NPs can serve as tumor-targeting T₁ MRI contrast agents with antioxidant effects.