A Preparation for High Aqueous Dispersion Fe 3 O 4 with Controllable Particle Size and Adjustable Aggregation State in a Magnetic Field

The conventional synthesis of superparamagnetic Fe 3 O 4 superparamagnetic nanoparticles (Fe 3 O 4 SNPs) for biomedical applications often suffers from poor aqueous dispersibility, complex multistep processes, and potential toxicity from organic solvents or surfactants. Achieving precise control over both particle size and magnetic field-driven aggregation state in a biocompatible manner remains a significant challenge. A facile one-pot hydrothermal synthesis strategy was developed using a polysaccharide-iron complex as the precursor to prepare nano-Fe 3 O 4 with excellent water dispersibility. With this method, we achieved precise regulation of Fe 3 O 4 particle size (3.2–12.5 nm) and magnetic field-driven aggregation behavior by optimizing reaction conditions (such as sugar content, NaOH concentration, and reaction time), making them suitable for different biomedical scenarios such as the separation of active ingredients, in vivo targeted delivery, or MRI contrast agent. The solution of synthesized Fe 3 O 4 SNPs remained stable at room temperature for up to six months without any precipitation and did not exhibit significant toxicity at different particle sizes. In vitro MRI performance evaluation revealed that Fe 3 O 4 SNPs with a particle size of 8.1 nm exhibited a high transverse relaxation rate (r2 = 189.8 mM –1 s –1 ) and a prominent r2/r1 ratio of 172.5, demonstrating potential as a T2 contrast agent; nanoparticles with a particle size of 4.0 nm displayed an r1 value approximately 1.6 times that of Gd-DTPA contrast agents, showing application potential as T1 contrast agents. This green synthesis method only uses water and polysaccharide iron complexes, thus providing a technical reference for the production of medical magnetic nanomaterials.