Engineering manganese ferrite shell on iron oxide nanoparticles for enhanced T₁ magnetic resonance imaging

Doping Mn (II) ions into iron oxide (IO) as manganese ferrite (MnIO) has been proved to be an effective strategy to improve T₁ relaxivity of IO nanoparticle in recent years; however, the high T₂ relaxivity of MnIO nanoparticle hampers its T₁ contrast efficiency and remains a hurdle when developing contrast agent for early and accurate diagnosis. Herein, we engineered the interfacial structure of IO nanoparticle coated with manganese ferrite shell (IO@MnIO) with tunable thicknesses. The Mn-doped shell significantly improve the T₁ contrast of IO nanoparticle, especially with the thickness of ∼0.8 nm. Compared to pristine IO nanoparticle, IO@MnIO nanoparticle with thickness of ∼0.8 nm exhibits nearly 2 times higher T₁ relaxivity of 9.1 mM^-1s^-1 at 3 T magnetic field. Moreover, exclusive engineering the interfacial structure significantly lower the T₂ enhancing effect caused by doped Mn (II) ions, which further limits the impairing of increased T₂ relaxivity to T₁ contrast imaging. IO@MnIO nanoparticles with different shell thicknesses reveal comparable T₁ relaxation rates but obvious lower T₂ relaxivities and r₂/r₁ ratios to MnIO nanoparticles with similar sizes. The desirable T₁ contrast endows IO@MnIO nanoparticle to provide sufficient signal difference between normal and tumor tissue in vivo. This work provides a detailed instance of interfacial engineering to improve IO-based T₁ contrast and a new guidance for designing effective high-performance T₁ contrast agent for early cancer diagnosis.