Ultrasmall Manganese Ferrites for In Vivo Catalase Mimicking Activity and Multimodal Bioimaging.

Manganese ferrite nanoparticles display interesting features in bioimaging and catalytic therapies. They have been recently used in theranostics as contrast agents in magnetic resonance imaging (MRI), and as catalase-mimicking nanozymes for hypoxia alleviation. These promising applications encourage the development of novel synthetic procedures to enhance the bioimaging and catalytic properties of these nanomaterials simultaneously. Herein, a cost-efficient synthetic microwave method is developed to manufacture ultrasmall manganese ferrite nanoparticles as advanced multimodal contrast agents in MRI and positron emission tomography (PET), and improved nanozymes. Such a synthetic method allows doping ferrites with Mn in a wide stoichiometric range (Mnx Fe3-x O4 , 0.1 ≤ x ≤ 2.4), affording a library of nanoparticles with different magnetic relaxivities and catalytic properties. These tuned magnetic properties give rise to either positive or dual-mode MRI contrast agents. On the other hand, higher levels of Mn doping enhance the catalytic efficiency of the resulting nanozymes. Finally, through their intracellular catalase-mimicking activity, these ultrasmall manganese ferrite nanoparticles induce an unprecedented tumor growth inhibition in a breast cancer murine model. All of these results show the robust characteristics of these nanoparticles for nanobiotechnological applications.

Heparin length in the coating of extremely small iron oxide nanoparticles regulates in vivo theranostic applications.

The positive contrast of extremely small iron oxide nanoparticles (ESIONP) in magnetic resonance imaging (MRI) rejuvenates this class of metal nanoparticles (NP).Yet, the current synthesis often lacks the possibility of adjusting the core size (while it is a key element for ESIONP-based MRI contrast behaviour), and also involved multiple complex steps before obtaining a ready-to-use probe for medical applications. In this study, we faced these challenges by applying heparin oligosaccharides (HO) of different lengths as coatings for the preparation of HEP-ESIONP with a one-pot microwave method. We demonstrated that the HO length could control the core size during the synthesis to achieve optimal positive MRI contrast, and that HEP-ESIONP were endowed directly with anticoagulant properties and/or a specific antitumor activity, according to the HO used. Relevantly, positron emission tomography (PET)-based in vivo biodistribution study conducted with 68Ga core-doped HEP-ESIONP analogues revealed significant changes in the probe behaviours, the shortening of HO promoting a shift from hepatic to renal clearance. The different conformations of HO coatings and a thorough in vitro characterisation of the probes' protein coronas provided insight into this crucial impact of HO length on opsonization-mediated immune response and elimination. Overall, we were able to identify a precise HO length to get an ESIONP probe showing prolonged vascular lifetime and moderate accumulation in a tumor xenograft, balanced with a low uptake by non-specific organs and favourable urinary clearance. This probe met all prerequisites for advanced theranostic medical applications with a dual MRI/PET hot spot capability and potential antitumor activity.