Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology is gradually emerging as an economically feasible and effective anti‐infection treatment. High‐entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high‐entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, monolayer HE MXenes are fabricated by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non‐high‐entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity (Km = 0.227 mm) and photothermal conversion efficiency (65.8%) in the second near‐infrared (NIR‐II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR‐II‐enhanced intrinsic oxidase mimic activity for killing methicillin‐resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by methicillin‐resistant Staphylococcus aureus as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug‐resistant bacterial infections and promote the healing of infected tissues.

Entropy‐Mediated High‐Entropy MXenes Nanotherapeutics: NIR‐II‐Enhanced Intrinsic Oxidase Mimic Activity to Combat Methicillin‐Resistant Staphylococcus Aureus Infection

On accounts of the advantages of inherent high stability, ease of preparation and superior catalytic activities, nanozymes have attracted tremendous potential in diverse biomedical applications as alternatives to natural enzymes. Optimizing the activity of nanozymes is significant for widening and boosting the applications into practical level. As the research of the catalytic activity regulation strategies of nanozymes is boosting, it is essential to timely review, summarize, and analyze the advances in structure-activity relationships for further inspiring ingenious research into this prosperous area. Herein, the activity regulation methods of nanozymes in the recent 5 years are systematically summarized, including size and morphology, doping, vacancy, surface modification, and hybridization, followed by a discussion of the latest biomedical applications consisting of biosensing, antibacterial, and tumor therapy. Finally, the challenges and opportunities in this rapidly developing field is presented for inspiring more and more research into this infant yet promising area.

Activity Regulating Strategies of Nanozymes for Biomedical Applications.

Metabolism is the sum of the enzyme-dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass in anabolic process, exhibiting high similarity in mammalian cell, microbial cell, and plant cell. Consequently, the loss or gain of metabolic enzyme activity will greatly affect cellular metabolism. Nanozymes, as emerging enzyme mimics with diverse functions and adjustable catalytic activities, has shown attractive potential for metabolic regulation. Although the basic metabolic tasks are highly similar for the cells from different species, the concrete metabolic pathway varies with the intracellular structure of different species. In this review, we describe the basic metabolism in living organisms and discuss the similarities and differences in the metabolic pathways among mammalian, microbial and plant cells and the regulation mechanism. We then systematically review the recent progress on regulation of cellular metabolism mainly including nutrients uptake and utilization, energy production and the accompanied redox reactions by different kinds of oxidoreductases and their applications in the field of disease therapy, antimicrobial therapy, and sustainable agriculture. Furthermore, the prospects and challenges of nanozymes in regulating cell metabolism are also discussed, which will broaden their application scenarios. This article is protected by copyright. All rights reserved.

Nanozyme-Based Regulation of Cellular Metabolism and their Applications.

Given the challenge of multidrug resistance in antibiotics, non-antibiotic-dependent antibacterial strategies show promise for anti-infective therapy. V2 C MXene-based nanomaterials have demonstrated strong biocompatibility and photothermal conversion efficiency (PCE) for photothermal therapy (PTT). However, the limitation of V2 C MXene's laser irradiation to the near-infrared region I (NIR-I) restricts tissue penetration, making it difficult to achieve complete bacterial eradication with single-effect therapeutic strategies. To address this, Pt nanoparticles (Pt NPs) were attached to V2 C, forming artificial nanoplatforms (Pt@V2 C). Pt@V2 C exhibited enhanced PCE (59.6%) and a longer irradiation laser (NIR-II) due to the surface plasmon resonance effect of Pt NPs and V2 C. Notably, Pt@V2 C displayed dual enzyme-like activity with chemodynamic therapy (CDT) and NIR-II enhanced dual enzyme-like activity. The biocatalytic mechanism of Pt@V2 C was elucidated using density functional theory. In an in vivo animal model, Pt@V2 C effectively eliminated methicillin-resistant Staphylococcus aureus from deep-seated tissues in subcutaneous abscesses and bacterial keratitis environments, accelerating abscess resolution and promoting wound and cornea healing through the synergistic effects of PTT/CDT. Transcriptomic analysis revealed that Pt@V2 C targeted inflammatory pathways, providing insight into its therapeutic mechanism. This study presents a promising therapeutic approach involving hyperthermia-amplified biocatalysis with Pt NPs and MXene nanocomposites. This article is protected by copyright. All rights reserved.

Platinum Nanoparticles Regulated V2 C MXene Nanoplatforms with NIR-II Enhanced Nanozyme Effect for Photothermal and Chemodynamic Anti-infective Therapy.

With the promotion of nanochemistry research, large numbers of nanomaterials have been applied in vivo to produce desirable cytotoxic substances in response to endogenous or exogenous stimuli for achieving disease-specific therapy. However, the performance of nanomaterials is a critical issue that is difficult to improve and optimize under biological conditions. The defective engineered nanoparticles have become the most researched hot materials in biomedical applications recently due to their excellent physicochemical properties, such as optical properties and redox reaction capabilities. Importantly, the properties of nanomaterials can be easily adjusted by regulating the type and concentration of defects in the nanoparticles without requiring other complex designs. Therefore, this tutorial review focuses on biomedical defect engineering and briefly discusses defect classification, introduction strategies, and characterization techniques. Several representative defective nanomaterials are especially discussed in order to reveal the relationship between defects and properties. A series of disease treatment strategies based on defective engineered nanomaterials are summarized. By summarizing the design and application of defective engineered nanomaterials, we hope to provide a simple but effective methodology for researchers to design and improve the therapeutic effects of nanomaterial-based therapeutic platforms from a materials science perspective. This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/adma.202304176

Defect Engineering in Biomedical Sciences.

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Single-Atom-Catalyzed MXene-Based nanoplatform with Photo-Enhanced Peroxidase-Like activity nanotherapeutics for Staphylococcus aureus infection

Two-dimensional NbS2 nanosheets with hyperthermia for killing bacteria to promote infected wound healing

Two-Dimensional Nbs2 Nanosheets with Hyperthermia for Eliminating Bacteria and Biofilm to Promote Infected Wound Healing