Near-Infrared Regulated Nanozymatic/Photothermal/Photodynamic Triple-Therapy for Combating Multidrug-Resistant Bacterial Infections via Oxygen-Vacancy Molybdenum Trioxide Nanodots.

Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen-vacancy molybdenum trioxide nanodots (MoO3-x NDs) are proposed as an efficient and safe bacteriostatic. The MoO3-x NDs alone possess triple-therapy synergistic efficiency based on the single near-infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase-like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad-spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO3-x NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H2 O2 (100 µm). The MoO3-x NDs show excellent antibacterial efficiency against drug-resistance extended spectrum ß-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO3-x NDs can effectively treat wounds infected with MRSA in living systems.

Heterostructure Nanozyme with Hyperthermia-Amplified Enzyme-Like Activity and Controlled Silver Release for Synergistic Antibacterial Therapy.

Heterostructure nanozymes as antibiotic-free antimicrobial agents exhibit great potential for multidrug-resistant (MDR) bacterial strains elimination. However, realization of heterostructure antimicrobials with enhanced interfacial interaction for synergistically amplified antibacterial therapy is still a great challenge. Herein, oxygen-vacancy-enriched glucose modified MoOx (G-MoOx) is exploited as a reducing agent to spontaneously reduce Ag (I) into Ag (0) that in situ grows onto the surface of G-MoOx. The resultant Ag doped G-MoOx (Ag/G-MoOx) heterostructure displays augmenting photothermal effect and NIR-enhanced oxidase-like activity after introducing Ag nanoparticles. What's more, NIR hyperthermia accelerate Ag+ ions release from Ag nanoparticles. Introduction of Ag greatly enhances antimicrobial activities of Ag/G-MoOx against MDR bacteria, especially the hybrid loading with 1 wt% Ag NPs exhibiting antibacterial efficacy up to 99.99% against Methicillin-resistant Staphylococcus aureus (MRSA, 1×106 CFU mL-1).

Bienzymatic synergism of vanadium oxide nanodots to efficiently eradicate drug-resistant bacteria during wound healing in vivo.

Antibiotic resistance is a common phenomenon observed during treatment with antibacterials. Use of nanozymes, especially those with synergistic enzyme-like activities, as antibacterials could overcome this problem, but their synthesis is limited by their high cost and/or complex production process. Herein, vanadium oxide nanodots (VOxNDs) were prepared via a one-step bottom-up ethanol-thermal method using vanadium trichloride as the precursor. VOxNDs alone possess bienzyme mimics of peroxidase and oxidase. Accordingly, highly efficient antibacterials against drug-resistant bacteria can be obtained through synergistic catalysis; the oxidase-like activity decomposes O2 to generate superoxide anion radical (O2-) and hydroxyl radicals (OH), and the intrinsic peroxidase-like activity can further induce the production of OH from external H2O2. Consequently, H2O2 concentration could decrease up to four magnitude orders with VOxNDs to achieve an antibacterial efficacy similar to that of H2O2 alone. Wound healing in vivo further confirms the high antibacterial efficiency, good biocompatibility, and application potential of the synergistic antibacterial system due to the "nano" structure of VOxNDs. The method of synthesis of nanodot antibacterials described in this paper is inexpensive, and the results of this study reveal the multi-enzymatic synergism of nanozymes.