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

Abstract

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 (MnxFe3‐xO4, 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.

Manganese‐Based Nanozymes: Preparation, Catalytic Mechanisms, and Biomedical Applications

“…For example, Qian et al have developed sheet-like MnO x on the surface of poly(lactic-co-glycolic acid)@polydopamine (PP) nanoparticles by co-precipitation using KMnO 4 as a raw material (Figure 2c). [44] [36] Copyright 2022, Wiley-VCH GmbH. b) Schematic diagram of the preparation process of Fe 3 O 4 @MnO x .…”

“…Considering that the tumor microenvironment (TME) usually contains a large number of endogenous H 2 O 2 and a severe hypoxic environment, Mnbased nanozymes with CAT-like activity are often used in tumor treatment strategies. [36,68,89] In a recent report, researchers doped Mn (II) ions into Ag 2 Se quantum dots to make a nanozyme. This nanozyme can accurately target TME, and the CAT-like activity of the Mn (II) component can rapidly convert H 2 O 2 into O 2 .…”

“…[ 4b ] Therefore, the selection of proper preparation methods is particularly important for Mn‐based nanozymes. In the past, the common methods for the preparation of Mn‐based nanozymes were the hydrothermal/solvothermal method, [ 33 ] chemical co‐precipitation method, [ 29,34 ] sol–gel method, [ 35 ] and other methods (e.g., microwave‐assisted method ( Figure a) [ 36 ] and ultrasonic precipitation method [ 37 ] ). The morphology, particle size, properties, and application areas of Mn‐based nanozymes are also very different due to different materials, methods, and reaction conditions.…”

“…Reproduced with permission. [ 36 ] Copyright 2022, Wiley‐VCH GmbH. b) Schematic diagram of the preparation process of Fe 3 O 4 @MnO x .…”

“…a) Schematic representation of the microwave-assisted method used to produce citrate-coated ultrasmall manganese ferrite with fine control in the chemical composition. Reproduced with permission [36]. Copyright 2022, Wiley-VCH GmbH.…”