Cu2 MoS4 Nanozyme with NIR-II Light Enhanced Catalytic Activity for Efficient Eradication of Multidrug-Resistant Bacteria.

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.

Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections.

The formation of bacterial biofilms closely associates with infectious diseases. Until now, precise diagnosis and effective treatment of bacterial biofilm infections are still in great need. Herein, a novel multifunctional theranostic nanoplatform based on MnO2 nanosheets (MnO2 NSs) has been designed to achieve pH-responsive dual-mode imaging and hypoxia-relief-enhanced antimicrobial photodynamic therapy (aPDT) of bacterial biofilm infections. In this study, MnO2 NSs were modified with bovine serum albumin (BSA) and polyethylene glycol (PEG) and then loaded with chlorin e6 (Ce6) as photosensitizer to form MnO2-BSA/PEG-Ce6 nanosheets (MBP-Ce6 NSs). After being delivered into the bacterial biofilm-infected tissues, the MBP-Ce6 NSs could be decomposed in acidic biofilm microenvironment and release Ce6 with Mn2+, which subsequently activate both fluorescence (FL) and magnetic resonance (MR) signals for effective dual-mode FL/MR imaging of bacterial biofilm infections. Meanwhile, MnO2 could catalyze the decomposing of H2O2 in biofilm-infected tissues into O2 and relieve the hypoxic condition of biofilm, which significantly enhances the efficacy of aPDT. An in vitro study showed that MBP-Ce6 NSs could significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in biofilms after 635 nm laser irradiation. Guided by FL/MR imaging, MRSA biofilm-infected mice can be efficiently treated by MBP-Ce6 NSs-based aPDT. Overall, MBP-Ce6 NSs not only possess biofilm microenvironment-responsive dual-mode FL/MR imaging ability but also have significantly enhanced aPDT efficacy by relieving the hypoxia habitat of biofilm, which provides a promising theranostic nanoplatform for bacterial biofilm infections.