CsPbBr3 Perovskite Nanoparticles causes Colitis-Like Symptom via Promoting Intestinal Barrier Damage and Gut Microbiota Dysbiosis.

Lead-based perovskite nanoparticles (Pb-PNPs) with superior optoelectronic properties are promising alternatives for the next generation of photovoltaics materials. This raises a great concern about their potential exposure toxicity in biological systems. However, little is known about their adverse effects on the gastrointestinal tract system so far. Here, the aim is to investigate the biodistribution, biotransformation, potential gastrointestinal tract toxicity, and effect on the gut microbiota after oral exposure to the CsPbBr3 perovskite nanoparticles (CPB PNPs). The advanced synchrotron radiation based microscopic X-ray fluorescence scanning and X-ray absorption near-edge spectroscopy demonstrate that high doses of CPB (CPB-H) PNPs can gradually transform into different lead-based compounds, subsequently accumulating in the gastrointestinal tract, especially the colon. Meanwhile, the pathological changes of stomach, small intestine, and colon reveal that CPB-H PNPs have higher gastrointestinal tract toxicity than Pb(Ac)2 , consequently leading to colitis-like symptoms. More importantly, 16S rRNA gene sequencing analysis discloses that CPB-H PNPs cause more significant alterations in the richness and diversity of the gut microbiota related to inflammation, intestinal barrier, and immune function than Pb(Ac)2 . The findings may contribute to shedding light on understanding the adverse effects on gastrointestinal tract and gut microbiota of Pb-PNPs.

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota.

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the "reactive oxygen species (ROS) storm" generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with "free radical sponge" fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the "ROS storm", but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.

Alleviation of Photoreceptor Degeneration Based on Fullerenols in rd1 Mice by Reversing Mitochondrial Dysfunction via Modulation of Mitochondrial DNA Transcription and Leakage.

Poor therapeutic outcomes of antioxidants in ophthalmologic clinical applications, including glutathione during photoreceptor degeneration in retinitis pigmentosa (RP), are caused by limited anti-oxidative capacity. In this study, fullerenols are synthesized and proven to be highly efficient in vitro radical scavengers. Fullerenol-based intravitreal injections significantly improve the flash electroretinogram and light/dark transition tests performed for 28 days on rd1 mice, reduce the thinning of retinal outer nuclear layers, and preserve the Rhodopsin, Gnat-1, and Arrestin expressions of photoreceptors. RNA-sequencing, RT-qPCR, and Western blotting validate that mitochondrial DNA (mt-DNA)-encoded genes of the electron transport chain (ETC), such as mt-Nd4l, mt-Co1, mt-Cytb, and mt-Atp6, are drastically downregulated in the retinas of rd1 mice, whereas nuclear DNA (n-DNA)-encoded genes, such as Ndufa1 and Atp5g3, are abnormally upregulated. Fullerenols thoroughly reverse the abnormal mt-DNA and n-DNA expression patterns of the ETC and restore mitochondrial function in degenerating photoreceptors. Additionally, fullerenols simultaneously repress Flap endonuclease 1 (FEN1)-mediated mt-DNA cleavage and mt-DNA leakage via voltage-dependent anion channel (VDAC) pores by downregulating the transcription of Fen1 and Vdac1, thereby inactivating the downstream pro-inflammatory cGAS-STING pathway. These findings demonstrate that fullerenols can effectively alleviate photoreceptor degeneration in rd1 mice and serve as a viable treatment for RP.

Aluminum hydroxide exposure induces neurodevelopmental impairment in hESC-derived cerebral organoids.

Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al, but the specific action on human brain development remains unclear. Al hydroxide (Al(OH)3), the most common vaccine adjuvant, is the major source of Al and poses risks to the environment and early childhood neurodevelopment. In this study, we explored the neurotoxic effect of 5 µg/ml or 25 µg/ml Al(OH)3 for six days on neurogenesis by utilizing human cerebral organoids from human embryonic stem cells (hESCs). We found that early Al(OH)3 exposure in organoids caused a reduction in the size, deficits in basal neural progenitor cell (NPC) proliferation, and premature neuron differentiation in a time and dose-dependent manner. Transcriptomes analysis revealed a markedly altered Hippo-YAP1 signaling pathway in Al(OH)3 exposed cerebral organoid, uncovering a novel mechanism for Al(OH)3-induced detrimental to neurogenesis during human cortical development. We further identified that Al(OH)3 exposure at day 90 mainly decreased the production of outer radial glia-like cells(oRGs) but promoted NPC toward astrocyte differentiation. Taken together, we established a tractable experimental model to facilitate a better understanding of the impact and mechanism of Al(OH)3 exposure on human brain development.

X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization.

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO2 ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn2 (CO)10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO2 . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2 , as the photolytic byproduct of Mn2 (CO)10 , has both glutathione (GSH) depletion and Fenton-like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.

Intercalation-Activated Layered MoO3 Nanobelts as Biodegradable Nanozymes for Tumor-Specific Photo-Enhanced Catalytic Therapy.

The existence of natural van der Waals gaps in layered materials allows them to be easily intercalated with varying guest species, offering an appealing strategy to optimize their physicochemical properties and application performance. Herein, we report the activation of layered MoO3 nanobelts via aqueous intercalation as an efficient biodegradable nanozyme for tumor-specific photo-enhanced catalytic therapy. The long MoO3 nanobelts are grinded and then intercalated with Na+ and H2 O to obtain the short Na+ /H2 O co-intercalated MoO3-x (NH-MoO3-x ) nanobelts. In contrast to the inert MoO3 nanobelts, the NH-MoO3-x nanobelts exhibit excellent enzyme-mimicking catalytic activity for generation of reactive oxygen species, which can be further enhanced by the photothermal effect under a 1064 nm laser irradiation. Thus, after bovine serum albumin modification, the NH-MoO3-x nanobelts can efficiently kill cancer cells in vitro and eliminate tumors in vivo facilitating with 1064 nm laser irradiation.

Plasmonic AuPt@CuS Heterostructure with Enhanced Synergistic Efficacy for Radiophotothermal Therapy.

Integrating multifunctional nanostructures capable of radiotherapy and photothermal ablation is an emerging alternative in killing cancer cells. In this work, we report a novel plasmonic heterostructure formed by decorating AuPt nanoparticles (NPs) onto the surfaces of CuS nanosheets (AuPt@CuS NSs) as a highly effective nanotheranostic toward dual-modal photoacoustic/computed tomography imaging and enhanced synergistic radiophotothermal therapy. These heterostructures can confer higher photothermal conversion efficiency via the local electromagnetic enhancement as well as a greater radiation dose deposition in the form of glutathione depletion and reactive oxygen species generation. As a result, the depth of tissue penetration is improved, and hypoxia of the tumor microenvironment is alleviated. With synergistic enhancement in the efficacy of photothermal ablation and radiotherapy, the tumor can be eliminated without later recurrence. It is believed that these multifunctional heterostructures will play a vital role in future oncotherapy with the enhanced synergistic effects of radiotherapy and photothermal ablation under the guided imaging of a potential dual-modality system.

Eco-Friendly and Scalable Synthesis of Fullerenols with High Free Radical Scavenging Ability for Skin Radioprotection.

Radiation dermatitis is a common but torturous side effect during radiotherapy, which greatly decreases the life quality of patients and potentially results in detrimental cessation of tumor treatment. Fullerenol, known as "free radical sponge," is a great choice for skin radioprotection because of its broad-spectrum free radical scavenging performance, good chemical stability, and biosafety. In this work, a facile scalable and eco-friendly synthetic method of fullerenols by catalyst assistant mechanical chemistry strategy is provided. As no organic solvent or high concentration of acid and alkali is introduced to this synthetic system, large-scale (>20 g) production of fullerenols with high yield (>95%) is obtained and no complicated purification is required. Then, the skin radioprotective performance of fullerenols is systematically explored for the first time. In vitro results indicate that fullerenols significantly block the reactive oxygen species-induced damage and enhance the viability of irradiated human keratinocyte cells. In vivo experiments suggest that medical sodium hyaluronate hydrogels loaded with fullerenols are suitable for skin administration and powerfully mitigate radiodermatitis via effectively protecting epidermal stem cells. The work not only provides an efficient gram-scale and eco-friendly synthetic method of fullerenols, but also promotes the development of fullerenols as potential skin radioprotectors.

Time-Resolved Activation of pH Sensing and Imaging in Vivo by a Remotely Controllable DNA Nanomachine.

Construction of probes or nanodevices capable of sensing pH with high spatial and temporal precision remains a challenge, despite their importance in monitoring of diverse physiological and pathological processes. Here we disclose the first remotely and noninvasively controlled DNA nanomachine that can monitor pH in live cells and animals in a temporally programmable manner. The nanomachine is designed by rational engineering of the DNA motif with a light-responsive element and further combination with an upconversion nanoparticle that works as a transducer to manipulate the nanomachine with the high precision of NIR light. The nanomachine not only allows for activated fluorescent imaging of intracellular pH, but it also can exert spatiotemporal control over its pH sensing activity in tumor-bearing mice by NIR light irradiation at a chosen time and place. This work illustrates the potential of combining DNA nanotechnology with upconversion tools to yield a precisely controlled nanomachine for temporally resolved pH sensing and imaging.

Self-Assembly of Copper-DNAzyme Nanohybrids for Dual-Catalytic Tumor Therapy.

Despite the great efforts of using DNAzyme for gene therapy, its clinical success is limited by the lack of simple delivery systems and limited anticancer efficacy. Here, we develop a simple approach for the synthesis of hybrid nanostructures that exclusively consist of DNAzyme and Cu2+ with ultra-high loading capacity. The Cu-DNAzyme nanohybrids allow to effectively co-deliver DNAzyme and Cu2+ into cancer cells for combinational catalytic therapy. The released Cu2+ can be reduced to Cu+ by glutathione and then catalyze endogenous H2 O2 to form cytotoxic hydroxyl radicals for chemodynamic therapy (CDT), while the 10-23 DNAzyme enables the catalytic cleavage of VEGFR2 mRNA and activates gene silencing for gene therapy. We demonstrate that the system can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity. Our work paves an extremely simple way to integrate DNAzyme with CDT for the dual-catalytic tumor treatment.

15 Years of Small: Research Trends in Nanosafety.

In the field of nano- and microscale science and technology, Small has become one of the worldwide leading journals since its initiation 15 years ago. Among all the topics covered in Small, "nanosafety" has received growing interest over the years, which accounts for a large proportion of the total publications of Small. Herein, inspired by its coming Special Issue "Rethinking Nanosafety," a general bibliometric overview of the nanosafety studies that have been published in Small is presented. Using the data derived from the Web of Science Core Collection, the annual publication growth, most influential countries/institutions as well as the visualized collaborations between different countries and institutions based on CiteSpace software are presented. A special emphasis on the impact of the previous Special Issue from Small that is related to nanosafety research is given and the research trend from the most highly cited papers during last 15 years is analyzed. Lastly, future research directions are also proposed.

Clinically Approved Carbon Nanoparticles with Oral Administration for Intestinal Radioprotection via Protecting the Small Intestinal Crypt Stem Cells and Maintaining the Balance of Intestinal Flora.

The exploration of an old drug for new biomedical applications has an absolute predominance in shortening the clinical conversion time of drugs for clinical application. In this work, carbon nanoparticles suspension injection (CNSI), the first clinically approved carbon nanoparticles in China, is explored as a new nano-radioprotective agent for potent intestinal radioprotection. CNSI shows powerful radioprotective performance in the intestine under oral administration, including efficient free radical scavenging ability, good biosafety, high chemical stability, and relatively long retention time. For example, CNSI shows high reactive oxygen species (ROS) scavenging activities, which effectively alleviates the mitochondrial dysfunction and DNA double-strand breaks to protect the cells against radiation-induced damage. Most importantly, this efficient ROS scavenging ability greatly helps restrain the apoptosis of the small intestinal epithelial and crypt stem cells, which decreases the damage of the mechanical barrier and thus relieves radiation enteritis. Moreover, CNSI helps remove the free radicals in the intestinal microenvironment and thus maintain the balance of intestinal flora so as to mitigate the radiation enteritis. The finding suggests a new application of clinically approved carbon nanoparticles, which not only promotes the development of new intestinal radioprotector, but also has a great potential for clinical transformation.

BiO2-x Nanosheets as Radiosensitizers with Catalase-Like Activity for Hypoxia Alleviation and Enhancement of the Radiotherapy of Tumors.

Tumor hypoxia is known to be one of the vital factors that aggravate tumor resistance to radiation therapy (RT) in which oxygen plays a critical role in tumor destruction. Herein, we synthesize a simple nanoradiosensitizer based on ultrathin BiO2-x nanosheets (NSs) modified with Tween 20 (T-BiO2-x NSs) to overcome the hypoxia-induced radioresistance as well as increase the efficacy of RT. On the one hand, bismuth as a high-Z element can effectively enhance the sensitivity of RT by depositing a higher radiation dose in tumors. The semiconductor property also endows its photocatalytic ability to produce extra reactive oxygen species (ROS) by reaction with the surrounding water. On the other hand, the defect-abundant BiO2-x NSs are also found to decompose the highly expressed hydrogen peroxide (H2O2) at the tumor site into oxygen (O2) for combating hypoxia. Both in vitro and in vivo experiments indicate that the as-prepared T-BiO2-x NSs could effectively inhibit tumor growth with X-ray irradiation. Our work thus provides a simple nanoradiosensitizer with multifunctionalities for increasing the RT efficacy while alleviating tumor hypoxia at the same time.

Tumor Microenvironment-Responsive Cu2(OH)PO4 Nanocrystals for Selective and Controllable Radiosentization via the X-ray-Triggered Fenton-like Reaction.

Traditional radiotherapy can induce injury to the normal tissue around the tumor, so the development of novel radiosensitizer with high selectivity and controllability that can lead to more effective and reliable radiotherapy is highly desirable. Herein, a new smart radiosensitizer based on Cu2(OH)PO4 nanocrystals that can simultaneously respond to endogenous stimulus (H2O2) and exogenous stimulus (X-ray) is reported. First, Cu2(OH)PO4 nanocrystals can generate CuI sites under X-ray irradiation through X-ray-induced photoelectron transfer process. Then, X-ray-triggered CuI sites serve as a catalyst for efficiently decomposing overexpressed H2O2 in the tumor microenvironment into highly toxic hydroxyl radical through the Fenton-like reaction, finally inducing apoptosis and necrosis of cancer cells. Meanwhile, this nonspontaneous Fenton-like reaction is greatly limited within normal tissues because of its oxygen-rich condition and insufficient H2O2 relative to tumor tissues. Thus, this strategy can ensure that the process of radiosentization can only be executed within hypoxic tumors but not in normal cells, resulting in the minimum damages to surrounding healthy tissues. As a result, the X-ray-triggered Fenton-like reaction via introducing nontoxic Cu2(OH)PO4 nanocrystals under the dual stimuli provides a more controllable and reliable activation approach to simultaneously enhance the radiotherapeutic efficacy and reduce side effects.

Nanoparticle Ligand Exchange and Its Effects at the Nanoparticle-Cell Membrane Interface.

The nanoparticle (nano)-cell membrane interface is one of the most important interactions determining the fate of nanoparticles (NPs), which can stimulate a series of biological events, allowing theranostic and other biomedical applications. So far, there remains a lack of knowledge about the mechanisms governing the nanoparticle-cell membrane interface, especially the impact of ligand exchange, in which molecules on the nanosurface become replaced with components of the cell membrane, resulting in unique interfacial phenomena. Herein, we describe a family of gold nanoparticles (AuNPs) of the same core size (∼13 nm core), modified with 12 different kinds of surface ligands, and the effects of their exchangeable ligands on both nanoparticle-supported lipid bilayers (SLBs) and nanoparticle-natural cell membrane interfaces. The ligands are categorized according to their molecular weight, charge, and bonding modes (physisorption or chemisorption). Importantly, we found that, depending on the adsorption affinity and size of ligand molecules, physisorbed ligands on the surface of NPs can be exchanged with lipid molecules. At a ligand exchange-dominated interface, the AuNPs typically aggregated into an ordered monolayer in the lipid bilayers, subsequently affecting cell membrane integrity, NP uptake efficiency, and the NP endocytosis pathways. These findings advance our understanding of the underlying mechanisms of the biological effects of nanoparticles from a new point of view and will aid in the design of novel, safe, and effective nanomaterials for biomedicine.

Nd3+ -Sensitized Upconversion Metal-Organic Frameworks for Mitochondria-Targeted Amplified Photodynamic Therapy.

Herein, we report the design and synthesis of a mitochondria-specific, 808 nm NIR light-activated photodynamic therapy (PDT) system based on the combination of metal-organic frameworks (MOFs) and upconversion photochemistry with an organelle-targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd3+ -sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser-irradiation-induced overheating effect. Furthermore, mitochondria-targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials.

Carbon monoxide (CO) therapy has emerged as a hot topic under exploration in the field of gas therapy as it shows the promise of treating various diseases. Due to the gaseous property and the high affinity for human hemoglobin, the main challenges of administrating medicinal CO are the lack of target selectivity as well as the toxic profile at relatively high concentrations. Although abundant CO releasing molecules (CORMs) with the capacity to deliver CO in biological systems have been developed, several disadvantages related to CORMs, including random diffusion, poor solubility, potential toxicity, and lack of on-demand CO release in deep tissue, still confine their practical use. Recently, the advent of versatile nanomedicine has provided a promising chance for improving the properties of naked CORMs and simultaneously realizing the therapeutic applications of CO. This review presents a brief summarization of the emerging delivery strategies of CO based on nanomaterials for therapeutic application. First, an introduction covering the therapeutic roles of CO and several frequently used CORMs is provided. Then, recent advancements in the synthesis and application of versatile CO releasing nanomaterials are elaborated. Finally, the current challenges and future directions of these important delivery strategies are proposed.

A Novel Drug Design Strategy: An Inspiration from Encaging Tumor by Metallofullerenol Gd@C82(OH)22.

Cancer remains a major threat to human health worldwide. Cytotoxicity has imposed restrictions on the conventional cytotoxic drug-based chemotherapy. The rapidly-developing nanomedicine has shown great promise in revolutionizing chemotherapy with improved efficiency and reduced toxicity. Gd@C82(OH)22, a novel endohedral metallofullerenol, was first reported by our research group to suppress tumor growth and metastasis efficiently without obvious toxicity. Gd@C82(OH)22 imprisons tumors by facilitating the formation of surrounding fibrous layers which is different from chemotherapeutics that poison tumor cells. In this review, the authors first reported the antineoplastic activity of metallofullerenol Gd@C82(OH)22 followed by further discussions on its new anti-cancer molecular mechanism-tumor encaging. On this basis, the unparalleled advantages of nanomedicine in the future drug design are discussed. The unique interaction modes of Gd@C82(OH)22 with specific targeted biomolecules may shed light on a new avenue for drug design. Depending on the surface characteristics of target biomolecules, nanomedicine, just like a transformable and dynamic key, can self-assemble into suitable shapes to match several locks for the thermodynamic stability, suggesting the target-tailoring ability of nanomedicine.

Functionalized MoS2 Nanovehicle with Near-Infrared Laser-Mediated Nitric Oxide Release and Photothermal Activities for Advanced Bacteria-Infected Wound Therapy.

The rising dangers of bacterial infections have created an urgent need for the development of a new generation of antibacterial nanoagents and therapeutics. A new near-infrared 808 nm laser-mediated nitric oxide (NO)-releasing nanovehicle (MoS2 -BNN6) is reported through the simple assembly of α-cyclodextrin-modified MoS2 nanosheets with a heat-sensitive NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6) for the rapid and effective treatment of three typical Gram-negative and Gram-positive bacteria (ampicillin-resistant Escherichia coli, heat-resistant Escherichia faecalis, and pathogen Staphylococcus aureus). This MoS2 -BNN6 nanovehicle has good biocompatibility and can be captured by bacteria to increase opportunities of NO diffusion to the bacterial surface. Once stimulated by 808 nm laser irradiation, the MoS2 -BNN6 nanovehicle not only exhibits photothermal therapy (PTT) efficacy but also can precisely control NO release, generating oxidative/nitrosative stress. The temperature-enhanced catalytic function of MoS2 induced by 808 nm laser irradiation simultaneously accelerates the oxidation of glutathione. This acceleration disrupts the balance of antioxidants, ultimately resulting in significant DNA damage to the bacteria. Within 10 min, the MoS2 -BNN6 with enhanced PTT/NO synergetic antibacterial function achieves >97.2% inactivation of bacteria. The safe synergetic therapy strategy can also effectively repair wounds through the formation of collagen fibers and elimination of inflammation during tissue reconstruction.

Synthesis of Surface-Modification-Oriented Nanosized Molybdenum Disulfide with High Peroxidase-Like Catalytic Activity for H2 O2 and Cholesterol Detection.

Abnormal H2 O2 and cholesterol levels are closely related to many diseases. This work reports a facile process for the synthesis of oxidized glutathione (GSSG)-modified MoS2 nanosheets (MoS2 -GSSG NSs). The biocompatible MoS2 -GSSG NSs have good dispersibility and high affinity to the substrate 3,3',5,5'-tetramethylbenzidine (TMB), which is beneficial for improving peroxidase-like catalytic activity of MoS2 . The high peroxidase-like activity of MoS2 -GSSG NSs was applied as a robust nanoplatform for low-cost, rapid, and highly effective colorimetric detection of H2 O2 and total/free cholesterol. Moreover, the peroxidase-like catalytic mechanism was studied by the steady-state kinetics method. The catalytic activity was remarkably high at a wide range of pH (2.4-7.0) and temperature values (25-70 °C). The cholesterol was catalyzed by cholesterol oxidase (ChOx) in the presence of O2 to generate H2 O2 , which oxidized TMB to generate a blue-colored product (oxTMB) under the catalysis of MoS2 -GSSG NSs. The detection limit (DL) of total cholesterol and H2 O2 was as low as 5.36 and 0.51 µm, respectively. The linear ranges for detecting cholesterol and H2 O2 were from 5.36 to 800 µm and from 0.51 to 50 µm, respectively. This method was also successfully applied to the detection of cholesterol in serum. The detection concentration of total cholesterol was consistent with that of the value detected by the blood biochemical method used in the clinic.