Enzymatically synthesised MnO2 nanoparticles for efficient near-infrared photothermal therapy and dual-responsive magnetic resonance imaging

Abstract

Manganese dioxide (MnO₂) nanoparticles (NPs) are highly attractive for biomedical applications due to their biocompatibility, stimuli-responsive magnetic resonance imaging (MRI) properties and capability to modulate the hypoxic tumour microenvironment (TME). However, conventional MnO₂ NPs do not possess photothermal therapy (PTT) functions except for hybrids with other photothermal materials. Herein, we first reveal the extraordinary photothermal conversion efficiency (44%) of enzymatically synthesised MnO₂ NPs (Bio-MnO₂ NPs), which are distinct from chemically synthesised MnO₂ NPs. In addition, the Bio-MnO₂ NPs revealed high thermal recycling stability and solubility as well as dual pH- and reduction-responsive MRI enhancement for tumour theragnosis. These NPs were prepared through a facile MnxEFG enzyme-mediated biomineralization process. The MnxEFG complex from Bacillus sp. PL-12 is the only manganese mineralization enzyme that could be heterologously overexpressed in its active form to achieve Bio-MnO₂ NPs without a bacterial host. The hexagonal layer symmetry of the Bio-MnO₂ NPs is the key feature facilitating the high photothermal conversion efficiency and TME-responsive T₁-weighted MRI. Evaluations both in vitro at the cellular level and in vivo in a systematic tumour-bearing mouse xenograft model demonstrated the high photothermal ablation efficacy of the Bio-MnO₂ NPs, which achieved complete tumour eradication with high therapeutic biosafety without obvious reoccurrence. Moreover, stimuli-responsive MR enhancement potentially allows imaging-guided precision PTT. With their excellent biocompatibility, mild synthesis conditions and relatively simple composition, Bio-MnO₂ NPs hold great translational promise.