Showing papers by "Hui Wei published in 2022"

A Valence-Engineered Self-Cascading Antioxidant Nanozyme for the Therapy of Inflammatory Bowel Disease.

Abstract: Antioxidant treatment strategy by scavenging reactive oxygen species (ROS) is a highly effective disease treatment option. Nanozymes with multiple antioxidant activities can cope with the diverse ROS environment. However, lack of design strategies and limitation of negative correlation for nanozymes with multiple antioxidant activities hindered their development. To overcome these difficulties, here we used ZnMn 2 O 4 as a model to explore the role of Mn valency at the octahedral site via a valence-engineered strategy, and found that its multiple antioxidant activities are positively correlated with the content of Mn 4+ . Therefore, through this strategy, a self-cascading antioxidant nanozyme LiMn 2 O 4 was constructed, and its efficacy was verified at the cellular level and in an inflammatory bowel disease model. This work not only provides guidance for the design of multiple antioxidant nanozymes, but also broadens the biomedical application potential of multiple antioxidant nanozymes.

Cerium oxide nanozyme attenuates periodontal bone destruction by inhibiting the ROS-NFκB pathway.

Abstract: Periodontitis, an inflammatory disease of oxidative stress, occurs due to excess reactive oxygen species (ROS) contributing to cell and tissue damage which in turn leads to alveolar bone resorption as well as the destruction of other periodontal support tissues. With significant recent advances in nanomaterials, we considered a unique type of nanomaterials possessing enzyme-like characteristics (called nanozymes) for potential future clinical applications, especially in light of the increasing number of studies evaluating nanozymes in the setting of inflammatory diseases. Here, we introduced a therapeutic approach for the management of periodontitis utilizing an injection of cerium oxide nanoparticles (CeO2 NPs) in situ. In this study, our synthesized CeO2 NPs could act as ROS scavengers in the inflammatory microenvironment with ideal outcomes. In vitro and in vivo experiments provide strong evidence on the roles of CeO2 NPs in scavenging multiple ROS and suppressing ROS-induced inflammation reactions stimulated by lipopolysaccharides. Moreover, CeO2 NPs could inhibit the MAPK-NFκB signalling pathway to suppress inflammatory factors. In addition, the results from a rat periodontitis model demonstrate that CeO2 NPs could exhibit a remarkable capacity to attenuate alveolar bone resorption, decrease the osteoclast activity and inflammation, and consequently improve the restoration of destroyed tissues. Collectively, our present study underscores the potential of CeO2 NPs for application in the treatment of periodontitis, and provides valuable insights into the application of nanozymes in inflammatory diseases.

Degradable ZnS-Supported Bioorthogonal Nanozymes with Enhanced Catalytic Activity for Intracellular Activation of Therapeutics.

Abstract: Bioorthogonal catalysis using transition-metal catalysts (TMCs) provides a toolkit for the in situ generation of imaging and therapeutic agents in biological environments. Integrating TMCs with nanomaterials mimics key properties of natural enzymes, providing bioorthogonal "nanozymes". ZnS nanoparticles provide a platform for bioorthogonal nanozymes using ruthenium catalysts embedded in self-assembled monolayers on the particle surface. These nanozymes uncage allylated profluorophores and prodrugs. The ZnS core combines the non-toxicity and degradability with the enhancement of Ru catalysis through the release of thiolate surface ligands that accelerate the rate-determining step in the Ru-mediated deallylation catalytic cycle. The maximum rate of reaction (Vmax) increases ∼2.5-fold as compared to the non-degradable gold nanoparticle analogue. The therapeutic potential of these bioorthogonal nanozymes is demonstrated by activating a chemotherapy drug from an inactive prodrug with efficient killing of cancer cells.

A Dopamine-Enabled Universal Assay for Catalase and Catalase-Like Nanozymes.

Abstract: Developing a universal strategy to measure catalase (CAT)/CAT-like activity, on one hand, overcomes limitations on current assays, such as moderate sensitivity and limited sample scope; on the other hand, facilitates insightful studies on applications of CAT and CAT-like nanozymes. Herein, the oxygen-sensitive and H2O2-inhibitory self-polymerization of dopamine (DA) was demonstrated as an activity indicator of CAT or CAT-like nanozymes, which monitors the catalytically generated O2 in a hypoxic environment. A typical assay for natural CAT was achieved under the optimized conditions. Moreover, this assay was suitable for diverse types of samples, ranging from nanozymes, animal tissues, to human saliva. By comparing the merits and limitations of common methods, this assay shows all-round advantages in sensitivity, specificity, and versatility, facilitating the formulation of measurement criteria and the development of potential standardized assays for CAT (or CAT-like nanozyme) activity.

Nanozyme-Enabled Treatment of Cardio- and Cerebrovascular Diseases.

Abstract: Cardio- and cerebrovascular diseases are two major vascular-related diseases that lead to death worldwide. Reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of diseases. Excessive ROS induce cellular context damage and lead to tissue dysfunction. Nanozymes, as emerging enzyme mimics, offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of ROS-related cardio- and cerebrovascular diseases by directly scavenging excess ROS or regulating pathologically related molecules. This review first introduces nanozyme-enabled therapeutic mechanisms at the cellular level. Then, the therapies for several typical cardio- and cerebrovascular diseases with nanozymes are discussed, mainly including cardiovascular diseases, ischemia reperfusion injury, and neurological disorders. Finally, the challenges and outlooks for the application of nanozymes are also presented. This review will provide some instructive perspectives on nanozymes and promote the development of enzyme-mimicking strategies in cardio- and cerebrovascular disease therapy.

Spinel-Oxide-Based Laccase Mimics for the Identification and Differentiation of Phenolic Pollutants.

Abstract: Phenol and its derivatives, known as persistent organic pollutants, have long threatened human health and environmental safety. There is an urgent need to develop convenient, low-cost, and multiplex analytical methods. Since phenols are substrates of laccase, they can be detected via laccase-catalyzed colorimetric assays. Nevertheless, the laccase-based assays cannot distinguish different phenols. Moreover, natural laccases suffer from high cost and low stability issues. To meet these needs, here we developed a laccase-like nanozyme sensor array for phenol detection and differentiation, which takes advantage of both nanozymes and cross-reactive sensor arrays. First, we examined a series of spinel-type transition metal oxides and found that manganese on octahedral sites profoundly affects the laccase-like activity of the materials. Based on the developed manganese-based spinel oxides (i.e., Mn3O4, Zn0.4Li0.6Mn2O4, and LiMn2O4), a colorimetric sensor array was constructed. The sensor array could effectively identify and discriminate phenol and its derivatives and showed good performance in the identification and differentiation of phenols in tap water samples. This work provides an important guidance for the development of laccase-like nanozymes and a promising methodology for pollutant monitoring.

Cerium‐Based Metal–Organic Framework with Intrinsic Haloperoxidase‐Like Activity for Antibiofilm Formation

Abstract: Biofilms adhering to surfaces have severe impacts on both public health and industry. Environmentally friendly strategies for combating biofilms are needed due to the biosafety issues brought by traditional commercial anti‐biofilm additives. Enzyme‐based strategies for biofilm treatment have attracted great research interest, but there is still a major challenge ahead due to the high economic cost and limited stability of natural enzymes. Inspired by the antifouling mechanism of natural haloperoxidase (HPO) secreted by marine algae, which catalyzes the oxidative bromination of bacterial quorum sensing signaling molecules, its artificial enzyme is proposed here in response to the situation mentioned above. A cerium‐based metal–organic framework (Ce‐MOF) is verified to possess HPO‐like activity. Based on its favorable enzyme‐like activity, the Ce‐MOF exhibits remarkable antibacterial and biofilm formation suppression abilities. This study not only expands the variety of HPO‐like artificial enzymes but also paves the way for the application prospect of Ce‐MOFs in water pipe cleaning and biofouling treatment.

Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn3O4 Nanozymes for Acute Kidney Injury Therapy.

Abstract: Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, Mn3O4 nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, Mn3O4 Nfs could protect HK2 cells through cascade ROS scavenging (dismutating ·O2- into H2O2 by superoxide dismutase-like activity and then decomposing H2O2 by catalase-like activity). Second, Mn3O4 Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia-reperfusion AKI murine models. Furthermore, Mn3O4 Nfs could be used for the T1-MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.

Nanoceria as an Electron Reservoir: Spontaneous Deposition of Metal Nanoparticles on Oxides and Their Anti-inflammatory Activities.

Abstract: Designing metal-metal oxide heteronanostructures with synergistic and superior activities (unattainable in the case of a single entity) is of great interest for a wide range of technological applications. Traditional synthetic strategies typically require reducing agents, stabilizing ligands, or high temperature reductive treatment to produce oxide-supported metals. Herein, a facile noble metal deposition strategy is developed to produce silver, gold, and platinum nanocrystals on the surface of hollow mesoporous cerium oxide nanospheres without any pretreatment. Unlike the galvanic replacement reaction, the developed protocol employs the innate reductive potential of CeO2 to produce a high density of ultrafine noble metal nanocrystals homogeneously immobilized onto the surface of CeO2 nanospheres. The multienzyme-like activities (i.e., superoxide dismutase-like and catalase-like) of CeO2@metal nanostructures, originating from CeO2 and metal nanoparticles, were effectively utilized for anti-inflammatory therapies in two in vivo models. This oxygen vacancy-mediated reduction strategy can be generalized to produce diverse metal-metal oxide nanostructures for a wide range of applications.

High-Throughput Colorimetric Analysis of Nanoparticle-Protein Interactions Based on the Enzyme-Mimic Properties of Nanoparticles.

Abstract: While an in-depth understanding of the biological behavior of engineered nanoparticles (NPs) is of great importance for their various applications, it remains challenging to quantitatively characterize NP-protein interactions in a simple and high-throughput manner. In the present work, we propose a new, colorimetric approach capable of quantitatively analyzing the adsorption of proteins onto the surface of NPs by their distinct peroxidase-mimic properties. Taking cationic AuNPs as an example, we demonstrate that this colorimetric method is capable of evaluating NP-protein interactions in a simple and high-throughput manner in multiwell plates. Important binding parameters (e.g., the binding affinity) of three different serum proteins (bovine serum albumin, transferrin, and lysozyme) as well as human serum to AuNPs with three different sizes (average diameters of 5, 10, and 15 nm) have been obtained. Based on a quantitative analysis of NP-protein interactions, we observe that the binding affinity and the inhibition efficiency of the nanozyme activity of AuNPs are strongly affected by the characteristics of proteins as well as the sizes of NPs. These results illustrate the great potential of the present colorimetric method as a simple, low-cost, and high-throughput platform for quantitatively investigating NP-protein interactions.

eg Occupancy as a Predictive Descriptor for Spinel Oxide Nanozymes.

Abstract: Functional nanomaterials offer an attractive strategy to mimic the catalysis of natural enzymes, which are collectively called nanozymes. Although the development of nanozymes shows a trend of diversification of materials with enzyme-like activity, most nanozymes have been discovered via trial-and-error methods, largely due to the lack of predictive descriptors. To fill this gap, this work identified eg occupancy as an effective descriptor for spinel oxides with peroxidase-like activity and successfully predicted that the eg value of spinel oxide nanozymes with the highest activity is close to 0.6. The LiCo2O4 with the highest activity, which is finally predicted, has achieved more than an order of magnitude improvement in activity. Density functional theory provides a rationale for the reaction path. This work contributes to the rational design of high performance nanozymes by using activity descriptors and provides a methodology to identify other descriptors for nanozymes.