Ultrasmall Superparamagnetic Iron Oxide Nanoparticles Synthesized by Micellar Approach as a Potential Dual-Mode T1-T2 Contrast Agent

Objective: A micellar approach is used to synthesize Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) with an average diameter of 3.4±0.5 nm, suitable for dual-mode T1T2 contrast agents. Methods: Micelles with 3.8 nm, measured by dynamic light scattering, were obtained by selforganizing the surfactant iron(III) dodecyl sulfate (IDS) in 1-octanol. IDS was prepared by replacing Na+ cation in sodium dodecyl sulfate molecule, and its critical micelle concentration (CMC) was measured by electrical conductivity. The USPIONs were synthesized in a biphasic system: IDS in octanol (55% above the CMC) and water containing NaBH4. Results: A yellow precipitate is immediately formed at the water/alcohol interface, rapidly changes to a black one, and transfers to the aqueous phase. The magnetite phase was confirmed by X-ray diffraction and Mössbauer spectroscopy. The magnetic behavior shows a major paramagnetic character with a weak ferromagnetic component at 5 K, the latter attributed to the interparticle couplings below its blocking temperature (TB = 35 K). The particles were coated with carboxymethyl dextran, showing an isoelectric point of 2.7 with electrokinetic potential around -30 mV in the physiological pH range. Magnetic relaxation measurements showed relaxivity values r1 = 0.17 mM^-1 s^-1 and r2 = 1.73 mM^-1 s^-1 (r2/r1 = 10) in a 3T field. These values infer that the ultrasmall size affects the interactions with the protons of the nearby water molecules. The r2 value decreases because the core magnetization decreases with size; r1 intensifies due to the high surface. Conclusion:The results show a system with high colloidal stability, non-cytotoxic, and potential application as T1-T2 dual-mode contrast agents.