Rapid generation of fragrant thermo-sensitive genic male sterile rice with enhanced disease resistance via CRISPR/Cas9.

MAIN CONCLUSION: The three, by mutagenesis produced genes OsPi21, OsXa5, and OsBADH2, generated novel lines exhibiting desired fragrance and improved resistance. Elite sterile lines are the basis for hybrid rice breeding, and rice quality and disease resistance become the focus of new sterile lines breeding. Since there are few sterile lines with fragrance and high resistance to blast and bacterial blight at the same time in hybrid rice production, we here integrated the simultaneous mutagenesis of three genes, OsPi21, OsXa5, and OsBADH2, into Zhi 5012S, an elite thermo-sensitive genic male sterile (TGMS) variety, using the CRISPR/Cas9 system, thus eventually generated novel sterile lines would exhibit desired popcorn-like fragrance and improved resistance to blast and bacterial blight but without a loss in major agricultural traits such as yield. Collectively, this study develops valuable germplasm resources for the development of two-line hybrid rice with disease resistance, which provides a way to rapid generation of novel TGMS lines with elite traits.

A New Age of Drug Delivery: A Comparative Perspective of Ferritin-Drug Conjugates (FDCs) and Antibody-Drug Conjugates (ADCs).

Ferritin-drug conjugates (FDCs) and antibody-drug conjugates (ADCs) respectively represent the innovative and traditional mainstream approaches in drug delivery systems, each offering unique advantages and challenges. This viewpoint delves into the evolving landscape of drug delivery technologies, specifically focusing on FDCs and ADCs. Each method exhibits unique advantages and inherent challenges, shaping their roles in therapeutic applications. The article provides a comparative analysis of two delivery systems, FDCs and ADCs, in terms of targeting accuracy, drug loading capacity, and the nature of the payload itself. This comparison offers valuable insights into the distinct advantages and disadvantages associated with each system, enabling a clearer understanding of their potential applications and limitations in therapeutic contexts. This analysis is crucial for optimizing the use of these delivery systems across varying medical contexts, offering a comprehensive overview of their impact on the field of drug delivery.

Regulating the N Coordination Environment of Co Single-Atom Nanozymes for Highly Efficient Oxidase Mimics.

Single-atom catalysts with well-defined atomic structures and precisely regulated coordination environments have been recognized as potential substitutes for natural metalloenzymes. Inspired by the metal coordination structure of natural enzymes, we show here that the oxidase-like activity of single-atom Co catalysts greatly depends on their local N coordination around the Co catalytic sites. We synthesized a series of Co single-atom catalysts with different nitrogen coordination numbers (Co-Nx(C), x = 2, 3, and 4) and demonstrated that the oxidase-like activity of single-atom Co catalysts could be effectively tailored by fine-tuning the N coordination. Among the studied single-atom Co catalysts, the Co-N3(C) with three-coordinate N atoms shows the optimum oxygen adsorption structure and robust reactive oxygen species (ROS) generation, thus presenting the preferable oxidase-like catalytic activity. This work facilitates the future development of rational nanozyme designs for targeting reactions at the atomic level.

Atomic-Level Regulation of Cobalt Single-Atom Nanozymes: Engineering High-Efficiency Catalase Mimics.

Nanozymes aim to mimic the highly evolved active centers of natural enzymes. Despite progress in nanozyme engineering, their catalytic performance is much less favorable compared with natural enzymes. This study shows that precise control over the atomic configuration of the active centers of Co single-atom nanozymes (SAzymes) enables the rational regulation of their catalase-like performance guided by theorical calculations. The constructed Co-N3 PS SAzyme exhibits an excellent catalase-like activity and kinetics, exceeding the representative controls of Co-based SAzymes with different atomic configurations. Moreover, we developed an ordered structure-oriented coordination design strategy for rationally engineering SAzymes and established a correlation between the structure and enzyme-like performance. This work demonstrates that precise control over the active centers of SAzymes is an efficient strategy to mimic the highly evolved active sites of natural enzymes.

Highly Sensitive and Selective Detection of Formaldehyde via Bio-Electrocatalysis over Aldehyde Dehydrogenase.

Formaldehyde (HCHO), as one of the prominent indoor pollutants, causes many health-related problems. Although the detection of HCHO is a widespread concern and a variety of detection methods have been continuously developed, the volatile organic chemical (VOC) interference remains to be solved. Here, we report a highly sensitive and selective method for HCHO detection, relying on the selective electrochemical oxidation of formaldehyde catalyzed by aldehyde dehydrogenases (ALDHs) on a Cu electrode. The detection signal exhibits a standard power law relationship against the analytes with a broad detection range of 10-5-10-15 M and a limit of detection (LOD) of 1.46 × 10-15 M, far below the indoor safe exposure limit (about 10-9 M) for formaldehyde. In comparison to the standard spectrophotometry method, the ALDH-based electrochemical method shows a much high specificity to formaldehyde among common VOCs, such as benzene, toluene, and xylene. This simple yet effective detection technique opens up a new path for developing advanced formaldehyde sensors with high sensitivity and selectivity.

Surface-Mediated Production of Complexed •OH Radicals and FeO Species as a Mechanism for Iron Oxide Peroxidase-Like Nanozymes.

Fe3 O4 nanoparticles (NPs) with intrinsic peroxidase-like properties have attracted significant interest, although limited information is available on the definite catalytic mechanism. Here, it is shown that both complexed hydroxyl radicals (•OH) and high-valent FeO species are attributed primarily to the peroxidase-like catalytic activity of Fe3 O4 NPs under acid conditions rather than only being caused by free •OH radicals generated through the iron-driven Fenton/Haber-Weiss reactions as previously thought. The low energy barrier of OO bond dissociation of H2 O2 /•OOH (0.14 eV) and the high oxidation activity of surface FeO (0 eV) due to the reduced state of Fe on the surface of Fe3 O4 NPs thermodynamically favor both the •OH and FeO pathways. By contrast, high-valent FeO species are the key intermediates in the catalytic cycles of natural peroxidase enzymes. Moreover, it is demonstrated that the enzyme-like activity of Fe3 O4 NPs can be rationally regulated by modulating the size, surface structure, and valence of active metal atoms in the light of this newly proposed nanozyme catalytic mechanism.

Ferritin: A Multifunctional Nanoplatform for Biological Detection, Imaging Diagnosis, and Drug Delivery.

Ferritins are spherical iron storage proteins within cells that are composed of a combination of 24 subunits of two types, heavy-chain ferritin (HFn) and light-chain ferritin (LFn). They autoassemble naturally into a spherical hollow nanocage with an outer diameter of 12 nm and an interior cavity that is 8 nm in diameter. In recent years, with the constantly emerging safety issues and the concerns about unfavorable uniformity and indefinite in vivo behavior of traditional nanomedicines, the characteristics of native ferritin nanocages, such as the unique nanocage structure, excellent safety profile, and definite in vivo behavior, make ferritin-based formulations uniquely attractive for nanomedicine development. To date, a variety of cargo molecules, including therapeutic drugs (e.g., cisplatin, carboplatin, paclitaxel, curcumin, atropine, quercetin, gefitinib, daunomycin, epirubicin, doxorubicin, etc.), imaging agents (e.g., fluorescence dyes, radioisotopes, and MRI contrast agents), nucleic acids (e.g., siRNA and miRNA), and metal nanoparticles (e.g., Fe3O4, CeO2, AuPd, CuS, CoPt, FeCo, Ag, etc.) have been loaded into the interior cavity of ferritin nanocages for a broad range of biomedical applications from in vitro biosensing to targeted delivery of cargo molecules in living systems with the aid of modified targeting ligands either genetically or chemically. We reported that human HFn could selectively deliver a large amount of cargo into tumors in vivo via transferrin receptor 1 (TfR1)-mediated tumor-cell-specific targeting followed by rapid internalization. By the use of the intrinsic tumor-targeting property and unique nanocage structure of human HFn, a broad variety of cargo-loaded HFn formulations have been developed for biological analysis, imaging diagnosis, and medicine development. In view of the intrinsic tumor-targeting property, unique nanocage structure, lack of immunogenicity, and definite in vivo behavior, human HFn holds promise to promote therapeutic drugs, diagnostic imaging agents, and targeting moieties into multifunctional nanomedicines.Since the report of the intrinsic tumor-targeting property of human HFn, we have extensively explored human HFn as an ideal nanocarrier for tumor-targeted delivery of anticancer drugs, MRI contrast agents, inorganic nanoparticles, and radioisotopes. In particular, by the use of genetic tools, we also have genetically engineered human HFn nanocages to recognize a broader range of disease biomarkers. In this Account, we systematically review human ferritins from characterizing their tumor-binding property and understanding their mechanism and kinetics for cargo loading to exploring their biomedical applications. We finally discuss the prospect of ferritin-based formulations to become next-generation nanomedicines. We expect that ferritin formulations with unique physicochemical characteristics and intrinsic tumor-targeting property will attract broad interest in fundamental drug research and offer new opportunities for nanomedicine development.

Panicle Apical Abortion 7 Regulates Panicle Development in Rice (Oryza sativa L.).

The number of grains per panicle significantly contributes to rice yield, but the regulatory mechanism remains largely unknown. Here, we reported a loss-of-function mutant, panicle apical abortion 7 (paa7), which exhibited panicle abortion and degeneration of spikelets on the apical panicles during the late stage of young panicle development in rice. High accumulations of H2O2 in paa7 caused programmed cell death (PCD) accompanied by nuclear DNA fragmentation in the apical spikelets. Map-based cloning revealed that the 3 bp "AGC" insertion and 4 bp "TCTC" deletion mutation of paa7 were located in the 3'-UTR regions of LOC_Os07g47330, which was confirmed through complementary assays and overexpressed lines. Interestingly, LOC_Os07g47330 is known as FRIZZY PANICLE (FZP). Thus, PAA7 could be a novel allele of FZP. Moreover, the severe damage for panicle phenotype in paa7/lax2 double mutant indicated that PAA7 could crosstalk with Lax Panicle 2 (LAX2). These findings suggest that PAA7 regulates the development of apical spikelets and interacts with LAX2 to regulate panicle development in rice.

Thermal Atomization of Platinum Nanoparticles into Single Atoms: An Effective Strategy for Engineering High-Performance Nanozymes.

Although great progress has been made in artificial enzyme engineering, their catalytic performance is far from satisfactory as alternatives of natural enzymes. Here, we report a novel and efficient strategy to access high-performance nanozymes via direct atomization of platinum nanoparticles (Pt NPs) into single atoms by reversing the thermal sintering process. Atomization of Pt NPs into single atoms makes metal catalytic sites fully exposed and results in engineerable structural and electronic properties, thereby leading to dramatically enhanced enzymatic performance. As expected, the as-prepared thermally stable Pt single-atom nanozyme (PtTS-SAzyme) exhibited remarkable peroxidase-like catalytic activity and kinetics, far exceeding the Pt nanoparticle nanozyme. The following density functional theory calculations revealed that the engineered P and S atoms not only promote the atomization process from Pt NPs into PtTS-SAzyme but also endow single-atom Pt catalytic sites with a unique electronic structure owing to the electron donation of P atoms, as well as the electron acceptance of N and S atoms, which simultaneously contribute to the substantial enhancement of the enzyme-like catalytic performance of PtTS-SAzyme. This work demonstrates that thermal atomization of the metal nanoparticle-based nanozymes into single-atom nanozymes is an effective strategy for engineering high-performance nanozymes, which opens up a new way to rationally design and optimize artificial enzymes to mimic natural enzymes.

Nanozymes: From New Concepts, Mechanisms, and Standards to Applications.

Nanozymes are nanomaterials with intrinsic enzyme-like characteristics that have been booming over the past decade because of their capability to address the limitations of natural enzymes such as low stability, high cost, and difficult storage. Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanozymes hold promise to serve as direct surrogates of traditional enzymes by mimicking and further engineering the active centers of natural enzymes. In 2007, we reported the first evidence that Fe3O4 nanoparticles (NPs) have intrinsic peroxidase-mimicking activity, and since that time, hundreds of nanomaterials have been found to mimic the catalytic activity of peroxidase, oxidase, catalase, haloperoxidase, glutathione peroxidase, uricase, methane monooxygenase, hydrolase, and superoxide dismutase. Uniquely, a broad variety of nanomaterials have been reported to simultaneously exhibit dual- or multienzyme mimetic activity. For example, Fe3O4 NPs show pH-dependent peroxidase-like and catalase-like activities; Prussian blue NPs simultaneously possess peroxidase-, catalase-, and superoxide dismutase-like activity; and Mn3O4 NPs mimic all three cellular antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Taking advantage of the physiochemical properties of nanomaterials, nanozymes have shown a broad range of applications from in vitro detection to replacing specific enzymes in living systems. With the emergence of the new concept of "nanozymology", nanozymes have now become an emerging new field connecting nanotechnology and biology. Since the landmark paper on nanozymes was published in 2007, we have extensively explored their catalytic mechanism, established the corresponding standards to quantitatively determine their catalytic activities, and opened up a broad range of applications from biological detection and environmental monitoring to disease diagnosis and biomedicine development. Here we mainly focus on our progress in the systematic design and construction of functionally specific nanozymes, the standardization of nanozyme research, and the exploration of their applications for replacing natural enzymes in living systems. We also show that, by combining the unique physicochemical properties and enzyme-like catalytic activities, nanozymes can offer a variety of multifunctional platforms with a broad of applications from in vitro detection to in vivo monitoring and therapy. For instance, targeting antibody-conjugated ferromagnetic nanozymes simultaneously provide three functions: target capture, magnetic separation, and nanozyme color development for target detection. We finally will address the prospect of nanozyme research to become "nanozymology". We expect that nanozymes with unique physicochemical properties and intrinsic enzyme-mimicking catalytic properties will attract broad interest in both fundamental research and practical applications and offer new opportunities for traditional enzymology.

Exosome-like Nanozyme Vesicles for H2O2-Responsive Catalytic Photoacoustic Imaging of Xenograft Nasopharyngeal Carcinoma.

Photoacoustic imaging (PAI) is an attractive imaging modality, which is promising for clinical cancer diagnosis due to its advantages on deep tissue penetration and fine spatial resolution. However, few tumor catalytic/responsive PAI strategies are developed. Here, we design an exosome-like nanozyme vesicle for in vivo H2O2-responsive PAI of nasopharyngeal carcinoma (NPC). The intrinsic peroxidase-like activity of graphene quantum dot nanozyme (GQDzyme) effectively converts the 2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form in the presence of H2O2. The oxidized ABTS exhibits strong near-infrared (NIR) absorbance, rendering it to be an ideal contrast agent for PAI. Thus, GQDzyme/ABTS nanoparticle is a novel type of catalytic PAI contrast agent, which is sensitive to H2O2 produced from NPC cells. Furthermore, we develop an approach to construct exosome-like nanozyme vesicle via biomimetic functionalization of GQDzyme/ABTS nanoparticle with natural erythrocyte membrane modified with folate acid. In vivo animal experiments demonstrated that this exosome-like nanozyme vesicle effectively accumulated in NPC and selectively triggered catalytic PAI for NPC. In addition, our nanozyme vesicle exhibits excellent biocompatibility and stealth ability for long blood circulation. Together, we demonstrate that GQDzyme/ABTS based exosome-like nanozyme vesicle is an ideal nanoplatform for developing deep-tissue tumor-targeted catalytic PAI in vivo.

H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection.

An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery.

Glutathione ligand self-assembly enables luminescence from Au15 nanoclusters for highly sensitive and selective monitoring of blood Pb(II) ions.

Lead Pb(II) ions is a cumulative toxicant that impacts several biological systems and poses severe harm to young children. Accurate Pb(II) ions monitoring is thus of paramount importance. Here, we present the synthesis and application of glutathione-capped Au15 nanoclusters (Au15(SG)13) as a luminescence probe for the accurate and selective monitoring of blood Pb(II). The introduction of Pb(II) ions triggers orderly self-assembly of Au15 nanoclusters, resulting in the formation of rigid shell around Au nuclei. This limits the localized vibration of the glutathione ligands and their interaction with water molecules, greatly reducing non-radiative energy loss, and thereby enhancing the photoluminescence signal. Consequently, Au15(SG)13 nanoclusters exhibit high sensitivity for Pb(II) detection. The detection signal displays a linear relationship with Pb(II) over a wide detection range (0-800 µg/L), demonstrating a substantial sensitivity of 35.29 µg/L. Moreover, the developed nanoclusters show superior selectivity for Pb(II) ions, distinguishing them from other prevalent heavy metals. This work pave the way for the development of advanced Pb(II) sensors with high sensitivity and selectivity.

Bioinspired Hierarchical Self-Assembled Nanozyme for Efficient Antibacterial Treatment.

Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanomaterials hold promise to mimic the highly evolved biological exquisite nanostructures and sophisticated functions. Here, inspired by the ubiquitous antibacterial nanostructures on the wing surfaces of some insects, a NiCo2 O4 nanozyme with self-adaptive hierarchical nanostructure is developed that can capture bacteria of various morphotypes via the physico-mechanical interaction between the nanostructure and bacteria. Moreover, the developed biomimetic nanostructure further exhibits superior peroxidase-like catalytic activity, which can catalytically generate highly toxic reactive oxygen species that disrupt bacterial membranes and induce bacterial apoptosis. Therefore, the mechano-catalytic coupling property of this NiCo2 O4 nanozyme allows for an extensive and efficient antibacterial application, with no concerns of antimicrobial resistance. This work suggests a promising strategy for the rational design of advanced antibacterial materials by mimicking biological antibiosis.

Optimizing the standardized assays for determining the catalytic activity and kinetics of peroxidase-like nanozymes.

Nanozymes are nanomaterials with enzyme-like catalytic properties. They are attractive reagents because they do not have the same limitations of natural enzymes (e.g., high cost, low stability and difficult storage). To test, optimize and compare nanozymes, it is important to establish fundamental principles and systematic standards to fully characterize their catalytic performance. Our 2018 protocol describes how to characterize the catalytic activity and kinetics of peroxidase nanozymes, the most widely used type of nanozyme. This approach was based on Michaelis-Menten enzyme kinetics and is now updated to take into account the unique physicochemical properties of nanomaterials that determine the catalytic kinetics of nanozymes. The updated procedure describes how to determine the number of active sites as well as other physicochemical properties such as surface area, shape and size. It also outlines how to calculate the hydroxyl adsorption energy from the crystal structure using the density functional theory method. The calculations now incorporate these measurements and computations to better characterize the catalytic kinetics of peroxidase nanozymes that have different shapes, sizes and compositions. This updated protocol better describes the catalytic performance of nanozymes and benefits the development of nanozyme research since further nanozyme development requires precise control of activity by engineering the electronic, geometric structure and atomic configuration of the catalytic sites of nanozymes. The characterization of the catalytic activity of peroxidase nanozymes and the evaluation of their kinetics can be performed in 4 h. The procedure is suitable for users with expertise in nano- and materials technology.

Arginine-Enhanced Antimicrobial Activity of Nanozymes against Gram-Negative Bacteria.

The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult-to-treat Gram-negative pathogens. Herein, it is shown that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L-arginine affords a potent treatment for infections with Gram-negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme is dramatically increased by ≈1000-fold after L-arginine stimulation. Specifically, the combination therapy enhances bacterial outer and inner membrane permeability and promotes intracellular reactive oxygen species (ROS) generation. Moreover, the metabolomic and transcriptomic results reveal that combination treatment leads to the increased ROS-mediated damage by inhibiting the tricarboxylic acid cycle and oxidative phosphorylation, thereby inducing an imbalance of the antioxidant and oxidant systems. Importantly, L-arginine dramatically significantly accelerates the healing of infected wounds in mouse models of multidrug-resistant peritonitis-sepsis and skin wound infection. Overall, this work demonstrates a novel synergistic antibacterial strategy by combining the antimicrobial nanozymes with L-arginine, which substantively facilitates the nanozyme-mediated killing of pathogens by promoting ROS production.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Fe3O4 magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent.

Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 µM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.

Recent progress in single-atom nanozymes research.

Single-atom nanozyme (SAzyme) is the hot topic of the current nanozyme research. Its intrinsic properties, such as high activity, stability, and low cost, present great substitutes to natural enzymes. Moreover, its fundamental characteristics, i.e., maximized atom utilizations and well-defined geometric and electronic structures, lead to higher catalytic activities and specificity than traditional nanozymes. SAzymes have been applied in many biomedical areas, such as anti-tumor therapy, biosensing, antibiosis, and anti-oxidation therapy. Here, we will discuss a series of representative examples of SAzymes categorized by their biomedical applications in this review. In the end, we will address the future opportunities and challenges SAzymes facing in their designs and applications.

Tumor microenvironment responsive T1-T2 dual-mode contrast agent Fe3O4@ZIF-8-Zn-Mn NPs for in vivo magnetic resonance imaging.

Activated T1-T2 contrast agents can effectively improve the sensitivity and diagnosis accuracy of magnetic resonance imaging (MRI), but the construction of such contrast agents still remains a great challenge. In this work, a pH- and glutathione (GSH)-responsive T1-T2 dual-mode contrast agent, Fe3O4@ZIF-8-Zn-Mn nanoparticles (NPs), with simple components was constructed via simply assembly of paramagnetic Mn2+ ions (as T1 contrast agent) and Fe3O4 NPs (as T2 contrast agent) into a pH- and GSH-sensitive Zn-zeolitic imidazole framework (ZIF-8) matrix. Under neutral conditions, Fe3O4@ZIF-8-Zn-Mn NPs show good stability and weak T1-T2 dual-mode MRI contrast effect (r1 = 0.82 mM-1 s-1, r2 = 21.28 mM-1 s-1) due to the magnetic interference between Fe3O4 NPs and paramagnetic Mn2+ ions. In contrast, under acidic environment (pH = 6.5-5.5) and in the present GSH (0-4 mM), Fe3O4@ZIF-8-Zn-Mn NPs can be disassembled and release Fe3O4 NPs and paramagnetic Mn2+ ions, which causes simultaneous recovery of T1 and T2 imaging performances with enhanced r1 and r2 relaxation values up to 6.9 and 9.9 times, respectively. Moreover, in vivo MRI experiments showed that after the intravenous injection of Fe3O4@ZIF-8-Zn-Mn NPs for about one hour, the T1-weighted imaging of the tumor site becomes brighter with T1 signal enhanced by about 31%, while the T2-weighted imaging of the tumor site becomes darker with T2 signal enhanced by nearly 30%, suggesting the great potential of Fe3O4@ZIF-8-Zn-Mn NPs to be used as a tumor microenvironment-responsive T1-T2 dual-mode contrast agent for sensitive tumor imaging.