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

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 T₁ 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 T₁-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 T₁ 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 T₁ contrast enhancement along with low r₂/r₁ 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.