Impact of gamma sterilization on surface chemistry and T2 relaxivity of citrate-coated iron oxide (Fe3O4) nanoparticles

Purpose: Iron oxide nanoparticles (IONPs) are efficient T2-weighted magnetic resonance imaging (MRI) contrast agents. While gamma irradiation is an optimal terminal sterilization method, its effects on product functionality require evaluation. Prior studies explored irradiated IONPs’ colloidal properties, but their contrast performance has received limited attention. This study investigates gamma irradiation’s effects on structural integrity, coating stability, and T2 relaxivity of citrate-coated IONPs. Methods: IONPs with a 24.6 nm core were functionalized with citrate (IONPs@Citrate) and irradiated using a 60Co source (1.095–1.216 kGy/hr) at 15, 25, and 50 kGy in air. Irradiated and matched unirradiated IONPs@Citrate controls were prepared at 0–62.5 µg mL-1 and suspended in 1.0% agarose. T2 relaxivities were quantified using a 1.5 T MRI with a multislice spin-echo sequence (TR = 2500 ms; TE = 10–160 ms; ΔTE = 10 ms). Pre- and post-irradiation characterizations included FTIR, XRD, and zeta potential to assess surface chemistry, crystalline structure, and colloidal stability, respectively. Results: Irradiated IONPs@Citrate exhibited aggregation and settling, indicating reduced colloidal stability. Coating degradation was corroborated by disappearing citrate FTIR bands and declining zeta potentials. XRD revealed intact magnetite cores, though 50 kGy particles showed a slight peak shift. T2 relaxivity significantly decreased post-irradiation (ANOVA, p < 0.001), with values declining from 2.37 mL • µg⁻¹·s⁻¹ in the unirradiated control to 1.08 mL • µg⁻¹·s⁻¹ at 50 kGy. Aggregation likely reduces the accessible surface area for water-nanoparticle interaction and dampens the local magnetic field, resulting in reduced T2 contrast. Conclusion: Gamma irradiation of IONPs@Citrate causes radiolytic degradation of the capping layer, leading to aggregation and diminished colloidal stability. Consequently, nanoparticle T2 relaxivity is significantly reduced. These results demonstrate that gamma irradiation compromises the relaxivity of IONPs@Citrate, highlighting the need to explore radiation-resistant coatings, (e.g., PEG, dextran) or alternative sterilization methods such as aseptic filtration or UV irradiation.