Coating Engineering of MnFe₂O₄ Nanoparticles with Superhigh T₂ Relaxivity and Efficient Cellular Uptake for Highly Sensitive Magnetic Resonance Imaging

Superparamagnetic nanoparticles with superhigh T₂ relaxivity and cellular uptake are strongly desired for ultrasensitive magnetic resonance imaging (MRI). Towards this end, highly monodispersed manganese ferrite nanoparticles (MNPs, 6 nm) with mPEG-g-PEI and PEG coatings as model system are employed in this study to investigate the coating engineering for simultaneously high T₂ relaxivity and cellular uptake. The quantitative evaluations of the intracellular uptake indicate that mPEG-g-PEI modified MNPs possess highly efficient cellular uptake, 2.4-fold larger than that with mPEG coating. More significantly, this coating simultaneously leads to a remarkably high T₂ relaxivity up to 331.8 mm^-1 s^-1, which is 4 times larger than that of the mPEG control and the largest value reported for superparamagnetic iron oxides with similar size. Modeling analysis reveals that the superior relaxivity is mainly attributed to the largely reduced diffusivity of water molecules trapped in the mPEG-g-PEI net. Further MRI of MDA-MB-231 breast cancer cells loaded MNPs with mPEG-g-PEI coating demonstrated the strong MR contrast in vitro effect with a T₂ relaxivity as high as 92.6 mm^-1 s^-1, 2.5-folds larger than reported 10 nm MNPs. This study provides a universal strategy of coating engineering of various magnetic nanoparticles for highly sensitive MRI.