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

摘要

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 T-1-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.