A Polyoxometalate-Based Pathologically Activated Assay for Efficient Bioorthogonal Catalytic Selective Therapy.

Since polyoxometalates (POMs) can undergo reversible multi-electron redox transformations, they have been used to modulate the electronic environment of metal nanoparticles for catalysis. Besides, POMs possess unique electronic structures and acid-responsive self-assembly ability. These properties inspired us to tackle the drawbacks of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction in biomedical applications, such as low catalytic efficiency and unsatisfactory disease selectivity. Herein, we construct molybdenum (Mo)-based POM nanoclusters doped with Cu (Cu-POM NCs) as a highly efficient bioorthogonal catalyst, which is responsive to pathologicallyacid and H2 S for selective antibiofilm therapy. Leveraging the merits of POMs, the Cu-POM NCs exhibit biofilm-responsive self-assembly behavior, efficient CuAAC-mediated in situ synthesis of antibacterial molecules, and a NIR-II photothermal effect selectively triggered by H2 S in pathogens. The consumption of bacterial H2 S at the pathological site by Cu-POM NCs extremely decreases the number of persisterbacteria, which is conducive to the inhibition of bacterial tolerance and elimination of biofilms. Unlocked at pathological sites and endowed with NIR-II photothermal property, the constructed POM-based bioorthogonal catalytic platform provides new insights into the design of efficient and selective bioorthogonal catalysts for disease therapy.

Nanozyme-Based Supramolecular Self-Assembly As an Artificial Host Defense System For Treatment of Bacterial Infections.

The proper functioning of host defense system (HDS) is the key to combating bacterial infection in biological organisms. However, the delicate HDS may be dysfunctional or dysregulated, resulting in persistent infection, tissue damage, or delayed wound healing. Herein, a powerful artificial "host defense system" (aHDS) is designed and constructed for treatment of bacterial infections. First, the aHDS can quickly trap the bacteria by electrostatic interactions. Next, the system can be stimulated to produce large amounts of cytotoxic reactive oxygen species (ROS) and exert strong antibacterial effects, which can further regulate the immune microenvironment, leading to macrophage polarization from M0 to pro-inflammatory phenotype (M1) for synergistic bacteria killing. At the later stages, the system can exhibit excellent antioxidant enzyme-like activities to reprogram the M1 macrophage to anti-inflammatory phenotype (M2) for accelerating wound healing. This powerful aHDS can effectively combat the bacteria and avoid excessive inflammatory responses for the treatment of bacteria-infected wounds.

COF-based artificial probiotic for modulation of gut microbiota and immune microenvironment in inflammatory bowel disease.

Conventional strategies for treating inflammatory bowel disease merely relieve inflammation and excessive immune response, but fail to solve the underlying causes of IBD, such as disrupted gut microbiota and intestinal barrier. Recently, natural probiotics have shown tremendous potential for the treatment of IBD. However, probiotics are not recommended for IBD patients, as they may cause bacteremia or sepsis. Herein, for the first time, we constructed artificial probiotics (Aprobiotics) based on artificial enzyme-dispersed covalent organic frameworks (COFs) as the "organelle" and a yeast shell as the membrane of the Aprobiotics to manage IBD. The COF-based artificial probiotics, with the function of natural probiotics, could markedly relieve IBD by modulating the gut microbiota, suppressing intestinal inflammation, protecting the intestinal epithelial cells, and regulating immunity. This nature-inspired approach may aid in the design of more artificial systems for the treatment of various incurable diseases, such as multidrug-resistant bacterial infection, cancer, and others.

Integrating Incompatible Nanozyme-Catalyzed Reactions for Diabetic Wound Healing.

Multi-nanozymes are widely applied in disease treatment, biosensing, and other fields. However, most current multi-nanozyme systems exhibit only moderate activity since reaction microenvironments of different nanozyme are often distinct or even incompatible. Conventional assemble strategies are inapplicable for designing multi-nanozymes consisting of incompatible nanozymes. Herein, a versatile fiber-based compartmentalization strategy is developed to construct multi-nanozyme system capable of simultaneously performing incompatible reactions. In this system, the incompatible nanozymes are spatially distributed in distinct compartmentalized fibers, where different microenvironments can be tailored by controlling the doping reagent, endowing each nanozymes with the preferential microenvironments to exhibit their highest activity. As a proof of concept, pH-incompatible peroxidase-like and catalase-like catalytic reactions are tested to verify the feasibility of this strategy. By doping with benzoic acid in the desired location, the two pH-incompatible nanozymes can work simultaneously without interference. Further, it is demonstrated that the oxygen supply and antimicrobial power of the integrated platform can be applied for accelerating diabetic wound healing. It is hoped that this work provides a way to integrate incompatible nanozyme and broadens the application potential of multi-nanozymes.