After explorations in a diversity of single-atom nanozymes (SAzymes), developing dual-centered SAzymes becomes a promising approach for superior catalytic performance. But confusing mechanisms including atomic coordination, spatial configuration, and metal–metal atom interaction hinder the development and design of SAzymes. Herein, a dual-centered Fe-Cu-N_x SAzyme exhibits excellent peroxidase (POD)- and catalase (CAT)-like activities with d-band center (ε_d) coordination of Fe and Cu in multiple reaction stages, which plays a critical role in the adsorption of H₂O₂ molecule and H₂O and O₂ release. Therefore, the d-band center coordination, which can be represented by ε_d(Fe)–ε_d(Cu) shifts, leads to the competition between one-side and bilateral adsorption, which determines the favorable reaction path with lower energy barriers. Based on experimental statistics, simulated formation energies, and reaction barriers, 3 configurations, Fe-Cu-N₆-I, Fe-Cu-N₈-II, and Fe-Cu-N₈-III, are modeled and validated. Impressively, configuration-dependent catalytic selectivity and the competition between one-side and bilateral adsorption can be unveiled by d-band center coordination paradigm analysis. Theoretical simulations suggest that the unsymmetrical charge distribution over the three Fe-Cu configurations could tune the adsorption strength compared with the counterparts FeN₄ and CuN₄. The present work provides a potential route for optimizing enzyme-like catalysis by designing the dual- or even triple-metal SAzymes, which demonstrates the large space to modulate the metal atomic configuration and interaction.

Single-atom nanozymes have attracted much attention as a new type of high-performance nanozymes. Compared with other nanozymes, single-atom nanozymes have become the most promising candidates for naturally-occurring enzymes due to their lower cost, better activity, more flexible preparation, higher atom utilization, and flexible compositional and structural modifications. Moreover, the catalytic activity of single-atom nanozymes can be precisely constructed by regulating the active center and synergistic environment. Advanced characterization techniques combined with theoretical calculations can accurately identify the enzyme-like active sites and deeply reveal structure-performance correlation. In this review, the active center and enzyme-like activities of single-atom nanozymes are comprehensively summarized along with the recent research advances in antitumor, neurological disorders, wound healing, and antimicrobial. Finally, we also explore the future opportunities and challenges for single-atom nanozymes in the design and applications.

Fluorescence imaging has become an essential tool in biomedical research. However, non-invasive deep-tissue three-dimensional optical in vivo imaging with the high spatiotemporal resolution is challenging due to the interaction between photons and tissues. Beam shaping has been used to tailor microscopy techniques to enhance microscope performance. The near-infrared window (NIR) between 700 and 1,700 nm, generally emphasized as the NIR-II (1,000–1,700 nm) window, has been developed into a promising bio-optical solution chosen as the lower interaction effect in this spectrum, showing potential in basic biological research and clinical application. In this review, we summarize the existing methods to increase penetration depth and extensively describe biological microscopy techniques, NIR-II spectral windows, and fluorophores. Strategies to improve bioimaging performance and NIR-II imaging applications are introduced. Based on the current research achievements, we elucidate the main challenges and provide some recommendations and prospects for deep tissue penetration fluorescence for future biomedical applications.

Bioorthogonal reactions have attained great interest and achievements in various fields since its first appearance in 2003. Compared to traditional chemical reactions, bioorthogonal chemical reactions mediated by transition metals catalysts can occur under physiological conditions in the living system without interfering with or damaging other biochemical events happening simultaneously. The idea of using nanomachines to perform precise and specific tasks in living systems is regarded as the frontier in nanomedicine. Bioorthogonal chemical reactions and nanozymes have provided new potential and strategies for nanomachines used in biomedical fields such as drug release, imaging, and bioengineering. Nanomachines, also called as intelligence nanorobots, based on nanozymes with bioorthogonal reactions show better biocompatibility and water solubility in living systems and perform controlled and adjustable stimuli-triggered response regarding to different physiological environments. In this review, we review the definition and development of bioorthogonal chemical reactions and describe the basic principle of bioorthogonal nanozymes fabrication. We also review several controlled and adjustable stimuli-triggered intelligence nanorobots and their potential in therapeutic and engineered applications. Furthermore, we summarize the challenges in the use of intelligence nanorobots based on nanozymes with bioorthogonal chemical reactions and propose promising vision in smart nanodevices along this appealing avenue of research.

Homeostasis of gut microbiota is extremely essential for maintaining nutrient metabolism and regulating immunological function. The increasing evidence suggests that inflammatory bowel disease (IBD) is strongly associated with dysregulation of gut microbiota. During activated inflammation, excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by inflammatory cells play a detrimental role in regulating IBD and gut microbiota. ROS/RNS cause damage to the surrounding tissues, including nutrient absorption disorders, intestinal dysmotility and barrier dysfunction. Meanwhile, ROS/RNS provide terminal electron receptors for anaerobic respiration and support the bloom of facultative anaerobes, eventually causing gut microbiota dysbiosis. Redox-active nanoparticles (NPs) with catalytic properties or enzyme-like activities can effectively scavenge ROS/RNS, and selectively target inflamed sites via ultrasmall size-mediated enhanced permeation and retention (EPR) effect, showing great potential to regulate IBD and maintain the homeostasis of gut microbiota. In addition, the widespread application of NPs in commercial products has increased their accumulation in healthy organisms, and the biological effects on normal microbiota resulting from long-term exposure of NPs to gastrointestinal tract also need attention.

It is challenging to develop molecular fluorophores in the second near-infrared (NIR-II) window with long wavelength emission and high brightness, which can improve the performance of biological imaging. Herein, we report a molecular engineering approach to afford NIR-II fluorophores with these merits based on fused-ring acceptor (FRA) molecules. Dioctyl 3,4-propylenedioxy thiophene (PDOT-C8) is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene (3-EHOT), leading to more than 20 times enhancement of brightness. The nanofluorophores (NFs) based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield (QY) of 0.39% (QY of IR-26 is 0.050% in dichloroethane as reference) and peak absorption coefficient of 14.5 × 10⁴ M^-1·cm^-1 in aqueous solutions, which are significantly higher than those of 3-EHOT based COTIC-4F NFs. It is found that PDOT-C8 can weaken intermolecular aggregation, enhance protection of molecular backbone from water, and decrease backbone distortion, beneficial for the high brightness. Compared with indocyanine green with same injection dose, CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.

Normal levels of oxygen free radicals play an important role in cellular signal transduction, redox homeostasis, regulatory pathways, and metabolic processes. However, radiolysis of water induced by high-energy radiation can produce excessive amounts of exogenous oxygen free radicals, which cause severe oxidative damages to all cellular components, disrupt cellular structures and signaling pathways, and eventually lead to death. Herein, we show that hybrid nanoshields based on single-layer graphene encapsulating metal nanoparticles exhibit high catalytic activity in scavenging oxygen superoxide(·O₂^-), hydroxyl (·OH), and hydroperoxyl (HO₂·) free radicals via electron transfer between the single-layer graphene and the metal core, thus achieving biocatalytic scavenging both in vitro and in vivo. The levels of the superoxide enzyme, DNA, and reactive oxygen species measured in vivo clearly show that the nanoshields can efficiently eliminate harmful oxygen free radicals at the cellular level, both in organs and circulating blood. Moreover, the nanoshieldslead to an increase in the overall survival rate of gamma ray-irradiated mice to up to 90%, showing the great potential of these systems as protective agentsagainst ionizing radiation.