Large-scale in situ self-assembly and doping engineering of zinc ferrite nanoclusters for high performance bioimaging

Iron oxide nanomaterials has good biocompatibility and safety, and has been used as contrast agents for magnetic resonance imaging (MRI). However, its clinical usefulness is hampered by its difficult preparation on large scale, its rapid clearance in vivo and low target tissue enrichment efficiency. Here, we report the synthesis of water-soluble, biocompatible, superparamagnetic non-stoichiometric zinc ferrite nanoclusters (nZFNCs) of approximately 50 g in a single batch using a one-pot synthesis technique. nZFNCs is a secondary cluster structure with a size of about 40 nm composed of zinc-doped iron oxide nanoparticles with a size of about 6 nm. The surface of nZFNCS is endowed with a large number of carboxyl groups as active sites. By simply controlling the synthesis process and adjusting the proportion of metal precursors, the amount of zinc doping can be controlled, while maintaining the same size to ensure similar pharmacokinetics. Compared with undoped, the magnetic responsiveness and relaxation efficiency of nZFNCs are significantly improved, and the transverse relaxation efficiency (r₂) can reach 425.5 mM^-1 s^-1 (doping amount x = 0.25), which is 7 times higher than that of commercial Resovist and 10 times higher than that of Feridex. In vivo imaging results also further confirmed the excellent contrast enhancement performance of the nanoclusters, which can achieve high contrast for more than 2 h in the liver. The advantage of this platform over comparable systems is that the contrast enhancement features are derived from simple techniques that do not require complex physical and chemical methods.