GSH‐Depleted PtCu3 Nanocages for Chemodynamic‐ Enhanced Sonodynamic Cancer Therapy

The ultrahigh concentration of glutathione (GSH) inside tumors destroys reactive oxygen species (ROS)‐based therapy, improving the outcome of chemodynamic therapy (CDT)‐enhanced sonodynamic therapy (SDT) by depleting GSH is full of great challenge. Herein, PtCu₃ nanocages are first reported as acting as a sonosensitizer with highly efficient ROS generation under ultrasound irradiation. In addition, PtCu₃ nanocages can act as horseradish peroxidase‐like nanozymes, catalyzing the decomposition of H₂O₂ into ^?OH under acidic conditions for CDT. Surprisingly, PtCu₃ nanocages can act as another kind of nanozyme, mimicking glutathione peroxidase (GSH‐Px), which plays an important role in accelerating GSH depletion by oxidizing molecules, further weakening the capacity of tumor cells scavenging ROS by GSH. Both in vitro and in vivo studies demonstrate that PtCu₃ nanocages perform well in reducing GSH level for CDT‐enhanced SDT. Moreover, utilizing the high absorption in the near‐infrared region and strong X‐ray attenuation ability, the PtCu₃ nanocages are able to conduct photoacoustic/computed tomography dual‐modal imaging‐guided combined cancer therapy. It is worth mentioning that PtCu₃ nanocages cause minimal toxicity to normal tissues at therapeutic doses. This work highlights the use of PtCu₃ nanocages for effective CDT‐enhanced SDT via GSH depletion.     

Defect-Rich Adhesive Molybdenum Disulfide/rGO Vertical Heterostructures with Enhanced Nanozyme Activity for Smart Bacterial Killing Application

Nanomaterials with intrinsic enzyme-like activities, namely “nanozymes,” are showing increasing potential as a new type of broad-spectrum antibiotics. However, their feasibility is still far from satisfactory, due to their low catalytic activity, poor bacterial capturing capacity, and complicated material design. Herein, a facile synthesis of a defect-rich adhesive molybdenum disulfide (MoS₂)/rGO vertical heterostructure (VHS) through a one-step microwave-assisted hydrothermal method is reported. This simple, convenient but effective method for rapid material synthesis enables extremely uniform and well-dispersed MoS₂/rGO VHS with abundant S and Mo vacancies and rough surface, for a performance approaching the requirements of practical application. It is demonstrated experimentally and theoretically that the as-prepared MoS₂/rGO VHS possesses defect and irradiation dual-enhanced triple enzyme-like activities (oxidase, peroxidase, and catalase) for promoting free-radical generation, owing to much more active edge sites exposure. Meanwhile, the VHS-achieved rough surface exhibits excellent capacity for bacterial capture, with elevated reactive oxygen species (ROS) destruction through local topological interactions. As a result, optimized efficacy against drug-resistant Gram-negative and Gram-positive bacteria can be explored by such defect-rich adhesive nanozymes, demonstrating a simple but powerful way to engineered nanozymes for alternative antibiotics.     

2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy

Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO₄ artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy-rich BiVO₄ nanosheets (abbreviated V_v-r BiVO₄ NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the V_v-r BiVO₄ NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O₂/O₂^•− and H₂O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, V_v-r BiVO₄ NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.     

A Tumor‐Microenvironment‐Activated Nanozyme‐Mediated Theranostic Nanoreactor for Imaging‐Guided Combined Tumor Therapy

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme‐mediated 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) loaded ABTS@MIL‐100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging‐guided combined tumor therapy. The as‐constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme‐mediated “two‐step rocket‐launching‐like” process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H₂O₂ level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor‐triggered PTT. More importantly, the H₂O₂‐activated and acid‐enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme‐involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.     

Fe3O4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice

Aging is a process associated with blood–brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe₃O₄ nanozymes on neurogenesis have rarely been studied. This study examined the effects of Fe₃O₄ nanozymes on neuronal differentiation in the dentate gyrus (DG) and BBB integrity of D-galactose-induced aged mice. Long-term treatment with Fe₃O₄ nanozymes (10 μg/mL diluted in ddH₂O daily) markedly increased the doublecortin (DCX) immunoreactivity and decreased BBB injury induced by D-galactose treatment. In addition, the decreases in the levels of antioxidant proteins including superoxide dismutase (SOD) and catalase as well as autophagy-related proteins such as Becin-1, LC3II/I, and Atg7 induced by D-galactose treatment were significantly ameliorated by Fe₃O₄ nanozymes in the DG of the mouse hippocampus. Furthermore, Fe₃O₄ nanozyme treatment showed an inhibitory effect against apoptosis in the hippocampus. In conclusion, Fe₃O₄ nanozymes can relieve neuroblast damage and promote neuroblast differentiation in the hippocampal DG by regulating oxidative stress, apoptosis, and autophagy.     

Switchable Nanozyme Activity of Porphyrins Intercalated in Layered Gadolinium Hydroxide

In this study, organo-inorganic nanohybrids LHGd-MTSPP with enzyme-like activity were prepared by in situ intercalation of anionic 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin and its complexes with Zn(II) and Pd(II) (MTSPP, M = 2H, Zn(II) and Pd(II)) into gadolinium layered hydroxide (LHGd). The combination of powder XRD, CHNS analysis, FT-IR, EDX, and TG confirmed the layered structure of the reaction products. The basal interplanar distances in LHGd-MTSPP samples were 22.3–22.6 Å, corresponding to the size of an intercalated tetrapyrrole molecule. According to SEM data, LHGd-MTSPP hybrids consisted of individual lamellar nanoparticles 20–50 nm in thickness. The enzyme-like activity of individual constituents, LHGd-Cl and sulfoporphyrins TSPP, ZnTSPP and PdTSPP, and hybrid LHGd-MTSPP materials, was studied by chemiluminescence analysis using the ABAP/luminol system in phosphate buffer solution. All the individual porphyrins exhibited dose-dependent antioxidant properties with respect to alkylperoxyl radicals at pH 7.4. The intercalation of free base TSPP porphyrin into the LHGd preserved the radical scavenging properties of the product. Conversely, in LHGd-MTSPP samples containing Zn(II) and Pd(II) complexes, the antioxidant properties of the porphyrins changed to dose-dependent prooxidant activity. Thus, an efficient approach to the design and synthesis of advanced LHGd-MTSPP materials with switchable enzyme-like activity was developed.     

Applications of Nanozymology in the Detection and Identification of Viral,Bacterial and Fungal Pathogens

Nanozymes are synthetic nanoparticulate materials that mimic the biological activities of enzymes by virtue of their surface chemistry. Enzymes catalyze biological reactions with a very high degree of specificity. Examples include the horseradish peroxidase, lactate, glucose, and cholesterol oxidases. For this reason, many industrial uses of enzymes outside their natural environments have been developed. Similar to enzymes, many industrial applications of nanozymes have been developed and used. Unlike the enzymes, however, nanozymes are cost-effectively prepared, purified, stored, and reproducibly and repeatedly used for long periods of time. The detection and identification of pathogens is among some of the reported applications of nanozymes. Three of the methodologic milestones in the evolution of pathogen detection and identification include the incubation and growth, immunoassays and the polymerase chain reaction (PCR) strategies. Although advances in the history of pathogen detection and identification have given rise to novel methods and devices, these are still short of the response speed, accuracy and cost required for point-of-care use. Debuting recently, nanozymology offers significant improvements in the six methodological indicators that are proposed as being key in this review, including simplicity, sensitivity, speed of response, cost, reliability, and durability of the immunoassays and PCR strategies. This review will focus on the applications of nanozymes in the detection and identification of pathogens in samples obtained from foods, natural, and clinical sources. It will highlight the impact of nanozymes in the enzyme-linked immunosorbent and PCR strategies by discussing the mechanistic improvements and the role of the design and architecture of the nanozyme nanoconjugates. Because of their contribution to world health burden, the three most important pathogens that will be considered include viruses, bacteria and fungi. Although not quite seen as pathogens, the review will also consider the detection of cancer cells and helminth parasites. The review leaves very little doubt that nanozymology has introduced remarkable advances in enzyme-linked immunosorbent assays and PCR strategies for detecting these five classes of pathogens. However, a gap still exists in the application of nanozymes to detect and identify fungal pathogens directly, although indirect strategies in which nanozymes are used have been reported. From a mechanistic point of view, the nanozyme technology transfer to laboratory research methods in PCR and enzyme-linked immunosorbent assay studies, and the point-of-care devices such as electronic biosensors and lateral flow detection strips, that is currently taking place, is most likely to give rise to no small revolution in each of the six methodological indicators for pathogen detection and identification. While the evidence of widespread research reports, clinical trials and point-of-care device patents support this view, the gaps that still exist point to a need for more basic research studies to be conducted on the applications of nanozymology in pathogen detection and identification. The multidisciplinary nature of the research on the application of nanozymes in the detection and identification of pathogens requires chemists and physicists for the design, fabrication, and characterization of nanozymes; microbiologists for the design, testing and analysis of the methodologies, and clinicians or clinical researchers for the evaluation of the methodologies and devices in the clinic. Many reports have also implicated required skills in mathematical modelling, and electronic engineering. While the review will conclude with a synopsis of the impact of nanozymology on the detection and identification of viruses, bacteria, fungi, cancer cells, and helminths, it will also point out opportunities that exist in basic research as well as opportunities for innovation aimed at novel laboratory methodologies and devices. In this regard there is no doubt that there are numerous unexplored research areas in the application of nanozymes for the detection of pathogens. For example, most research on the applications of nanozymes for the detection and identification of fungi is so far limited only to the detection of mycotoxins and other chemical compounds associated with fungal infection. Therefore, there is scope for exploration of the application of nanozymes in the direct detection of fungi in foods, especially in the agricultural production thereof. Many fungal species found in seeds severely compromise their use by inactivating the germination thereof. Fungi also produce mycotoxins that can severely compromise the health of humans if consumed.     

An Ultrasmall SnFe2O4 Nanozyme with Endogenous Oxygen Generation and Glutathione Depletion for Synergistic Cancer Therapy

The tumor microenvironment (TME) with the characteristics of severe hypoxia, overexpressed glutathione (GSH), and high levels of hydrogen peroxide (H₂O₂) dramatically limits the antitumor efficiency by monotherapy. Herein, a novel TME-modulated nanozyme employing tin ferrite (SnFe₂O₄, abbreviated as SFO) is presented for simultaneous photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The as-fabricated SFO nanozyme demonstrates both catalase-like and GSH peroxidase-like activities. In the TME, the activation of H₂O₂ leads to the generation of hydroxyl radicals (•OH) in situ for CDT and the consumption of GSH to relieve antioxidant capability of the tumors. Meanwhile, the nanozyme can catalyze H₂O₂ to generate oxygen to meliorate the tumor hypoxia, which is beneficial to achieve better PDT. Furthermore, the SFO nanozyme irradiated with 808 nm laser displays a prominent phototherapeutic effect on account of the enhanced photothermal conversion efficiency (η  = 42.3%) and highly toxic free radical production performance. This “all in one” nanozyme integrated with multiple treatment modalities, computed tomography, and magnetic resonance imaging properties, and persistent modulation of TME exhibits excellent tumor theranostic performance. This strategy may provide a new dimension for the design of other TME-based anticancer strategies.     

NIR Laser-Triggered Microneedle-Based Liquid Band-Aid for Wound Care

Microneedles (MNs) have attracted widespread scientific and industrial interest in the past decade as an efficient, painless, low-cost, and relatively safe transdermal drug delivery device. However, their drawbacks such as insufficient dose accuracy and limited penetration depth may limit the clinical applications. Here, a light-controlled liquid band-aid based on MNs is developed for antibacterial applications. Metal–organic framework-derived peroxidase-like nanozyme loaded in MNs can not only convert light energy into heat to enhance drug permeation but also decompose hydrogen peroxide into hydroxyl radicals for antibacteria. The heat generated by the nanozyme can facilitate MNs to melt and form a liquid band-aid, which is beneficial to insulate the wound from the surrounding bacterial environment. These studies in a Staphylococcus aureus-infected mice model also prove that this laser-triggered liquid band-aid can efficiently reduce skin inflammation and promote wound healing. Together, these results demonstrate that the rational design of MNs can enhance antibacterial and wound healing efficiency.     

Development of Nanozymes for Food Quality and Safety Detection: Principles and Recent Applications

The public concerns about agrifood safety call for innovative and reformative analytical techniques to meet the inspection requirements of high sensitivity, specificity, and reproducibility. Enzyme‐mimetic nanomaterials or nanozymes, which combine enzyme‐like properties with nanoscale features, emerge as an excellent tool for quality and safety detection in the agrifood sector, due to not only their robust capacity in detection but also their attraction in future‐oriented exploitations. However, in‐depth understanding about the fundamental principles of nanozymes for food quality and safety detection remains limited, which makes their applications largely empirical. This review provides a comprehensive overview of the principles, designs, and applications of nanozyme‐based detection technique in the agrifood industry. The discussion mainly involves three mimicking types, that is, peroxidase, oxidase, and catalase‐like nanozymes, capable of detecting major agrifood analytes. The current principles and strategies are classified and then discussed in details through discriminating the roles of nanozymes in diverse detection platforms. Thereafter, recent applications of nanozymes in detecting various endogenous ingredients and exogenous contaminants in foods are reviewed, and the outlook of profound developments are explained. Evidenced by the increasing publications, nanozyme‐based detection techniques are narrowing the gap to practical‐oriented food analytical methods, while some challenges in optimization of nanozymes, diversification of recognition‐to‐signal manners, and sustainability of methodology need to conquer in the future.