Synthesis and characterization of nickel ferrite (NiFe₂O₄) nanoparticles as dual T₁–T₂ MRI contrast agents

Abstract

Dual-mode ( T₁ – T₂ ) magnetic resonance imaging (MRI) contrast agents offer improved diagnostic capability through simultaneous longitudinal and transverse relaxation enhancement. In this work, quasi-spherical and cubic NiFe₂O₄ nanoparticles were synthesized via a hydrothermal process by varying reaction time and subsequently coated with polyethylene glycol (PEG) to enhance colloidal stability. The quasi-spherical nanoparticles synthesized for 12 h exhibited an average diameter of ∼25 nm and a saturation magnetization (Mₛ) of 49 emu·g−1, whereas the cubic nanoparticles obtained after 24 h displayed an edge length of ∼65 nm with Mₛ = ∼ 67 emu·g−1. T₁ - and T₂ -weighted MRI measurements revealed that particle size and surface modification strongly influenced relaxivity. The 25 nm sample showed optimal dual-mode performance, with r₁ = 5.7 mM−1·s−1 and r₂ = 103.1 mM−1·s−1 ( r₂ / r₁ = ∼18), while PEG coating slightly reduced both relaxivities due to magnetic shielding but significantly improved dispersion stability. 65 nm cubic nanoparticles exhibited high r₂ (153.4 mM−1·s−1), confirming their suitability for T₂ -weighted imaging. In vitro MTT cytotoxicity assays on HepG2 cells at 200 μg·mL−1 demonstrated low toxicity, with cell viability exceeding 80 % after 72 h across all samples and > 94 % for PEG-coated variants. These results demonstrate that controlled morphology and surface engineering of NiFe₂O₄ nanoparticles can effectively tune their magnetic and relaxometric properties, enabling their application as efficient T₁–T₂ dual-mode MRI contrast agents. © 2025 Elsevier B.V.