Synthesis of BSA-Coated Iron Oxide Nanoparticles with Size Control for High-Performance T1 Contrast Agents in Magnetic Resonance Imaging

The excellent biocompatibility and favorable physicochemical properties of iron oxide nanoparticles have made them attractive candidates for magnetic resonance imaging. However, it remains challenging to synthesize high-performance <i>T</i>₁ contrast agents with controlled sizes and biocompatible coating materials. In this study, we demonstrate a simple and environmentally friendly approach for synthesizing ultra-small iron oxide nanoparticles using bovine serum albumin (BSA) as a template. Following synthesis, the iron oxide nanoparticles (Fe₃O₄) were oxidized to Fe₂O₃ via the addition of hydrogen peroxide, which resulted in enhanced <i>T</i>₁-weighted magnetic resonance contrast. The use of BSA not only stabilized the nanoparticles but also enabled precise control over nanoparticle size by adjusting the Fe-to-BSA molar ratio. This method yielded highly uniform and crystalline ultra-small nanoparticles ranging from approximately 3.7 to 7.9 nm in diameter. The <i>T</i>₁ contrast performance of the Fe₂O₃@BSA nanoparticles was evaluated at 3 T magnetic field. Among the synthesized samples, nanoparticles with sizes of 4.6 nm exhibited the strongest <i>T</i>₁ contrast enhancement along with low <i>r</i>₂/<i>r</i>₁ ratios. These features highlight their potential as promising alternatives to gadolinium-based contrast agents. In addition to their superior performance, this synthesis method is low-cost and non-toxic, making it suitable for scalable biomedical applications.