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Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag+ in the bacterial microenvironment. Here, we report a porous metal−organic framework (MOF)-based Zr-2-amin-1,4-NH2-benzenedicarboxylate@Ag (denoted as UiO-66-NH2-Ag) nanocomposite using an in-situ immobilization strategy where Ag NPs were fixed on the UiO-66-NH2 for improving the dispersion and utilization of Ag NPs. As a result, the reduced use dose of Ag NPs largely improves the biosafety of the UiO-66-NH2-Ag. Meanwhile, after activation by the Ag NPs, the UiO-66-NH2-Ag can act as nanozyme with high peroxidase (POD)-like activity to efficiently catalyze the decomposition of H2O2 to extremely toxic hydroxyl radicals (·OH) in the bacterial microenvironment. Simultaneously, the high POD-like activity synergies with the controllable Ag+ release leads to enhanced reactive oxygen species (ROS) generation, facilitating the death of resistant bacteria. This synergistic antibacterial strategy enables the low concentration (12 μg/mL) of UiO-66-NH2-Ag to achieve highly efficient inactivation of ampicillin-resistant Escherichia coli (AmprE. coli) and endospore-forming Bacillus subtilis (B. subtilis). In vivo results illustrate that the UiO-66-NH2-Ag nanozyme has a safe and accelerated bacteria-infected wound healing. [ABSTRACT FROM AUTHOR]

Abnormal H2O2 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 H2O2 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 H2O2, 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 H2O2 was as low as 5.36 and 0.51 μm, respectively. The linear ranges for detecting cholesterol and H2O2 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. Oxidized glutathione (GSSG)‐modified MoS2 nanosheets (MoS2‐GSSG NSs) that have good biocompatibility and dispersibility and high peroxidase‐like catalytic activity over a wide pH value and temperature range were simply constructed (see scheme). The MoS2‐GSSG NSs were applied as a robust nanoplatform for low‐cost, rapid, and highly effective colorimetric detection of H2O2 and cholesterol. [ABSTRACT FROM AUTHOR]

MoS2 nanoflakes (MoS2 NFs) with a diameter of ∼390 nm were obtained by a facile one-pot hydrothermal method and the NFs exhibited intrinsic peroxidase-like activity. After being modified by commonly used biocompatible surfactants including polyethyleneimine (PEI), polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), and cysteine (Cys), the peroxidase-like catalytic activities of MoS2 NFs were investigated by using 3,3′,5,5′-tetramethylbenzidine (TMB) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS) as chromogenic substrates. Compared to the polymer modified MoS2 NFs, Cys functionalized MoS2 NFs exhibited a high catalytic activity toward H2O2 in the presence of TMB or ABTS. Zeta potential and Michaelis–Menten analyses implied that the electrostatic force induced affinity or repulsion between the MoS2 NFs and substrates, as well as surface modifications of the MoS2 NFs played a key role in the catalytic reactions. Notably, a new peroxidase-like catalytic reaction mechanism was proposed based on the formation of a transient state of Cys–MoS2 NFs containing H2O2 and ABTS, and the catalytic reaction could occur because the Cys on the surface of the MoS2 NFs served as an electron transfer bridge between H2O2 and ABTS. Based on this finding, we also established a platform for colorimetric detection of H2O2 and glucose using Cys–MoS2 NFs as a peroxidase substitution. The limit of detection (LOD) was determined to be 4.103 μmol L−1 for H2O2, and the linear range (LR) was from 0 to 0.3 mmol L−1. The LOD for glucose was 33.51 μmol L−1 and the LR was from 0.05 to 1 mmol L−1, which is suitable for biomedical diagnosis. This work provides a new insight into the catalytic mechanism of peroxidase-like MoS2 NFs, and paves the way for enzyme-like nanomaterials to be used for medical diagnosis. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • hESC-derived organoid is an ideal model to evaluate the toxicity of Al(OH) 3. • Al(OH) 3 exposure at an early stage inhibited NPC proliferation. • Al(OH) 3 exposure at a later stage promoted NPC toward astrocyte differentiation. • Hippo-YAP1 signaling pathway is involved in Al(OH) 3 -induced impaired neurogenesis. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag + in the bacterial microenvironment. Here, we report a porous metal-organic framework (MOF)-based Zr-2-amin-1,4-NH 2 -benzenedicarboxylate@Ag (denoted as UiO-66-NH 2 -Ag) nanocomposite using an in-situ immobilization strategy where Ag NPs were fixed on the UiO-66-NH 2 for improving the dispersion and utilization of Ag NPs. As a result, the reduced use dose of Ag NPs largely improves the biosafety of the UiO-66-NH 2 -Ag. Meanwhile, after activation by the Ag NPs, the UiO-66-NH 2 -Ag can act as nanozyme with high peroxidase (POD)-like activity to efficiently catalyze the decomposition of H 2 O 2 to extremely toxic hydroxyl radicals (·OH) in the bacterial microenvironment. Simultaneously, the high POD-like activity synergies with the controllable Ag + release leads to enhanced reactive oxygen species (ROS) generation, facilitating the death of resistant bacteria. This synergistic antibacterial strategy enables the low concentration (12 μg/mL) of UiO-66-NH 2 -Ag to achieve highly efficient inactivation of ampicillin-resistant Escherichia coli (Amp r E. coli ) and endospore-forming Bacillus subtilis ( B. subtilis ). In vivo results illustrate that the UiO-66-NH 2 -Ag nanozyme has a safe and accelerated bacteria-infected wound healing.

In this work, BaYF 5 :20%Yb 3+ /2%Er 3+ / x %Bi 3+ (abbreviated as BaYF 5 :Yb,Er,Bi x , where x = 0-3.0) upconversion nanoparticles (UCNPs) with various doping concentrations of Bi 3+ were synthesized through a simple hydrothermal method. The influence of the doping amount of Bi 3+ on the microstructures and upconversion luminescence (UCL) properties of the BaYF 5 :Yb,Er,Bi x UCNPs was studied in detail. The doping concentration of Bi 3+ has little influence on the microstructures of the UCNPs but significantly impacts their UCL intensities. Under excitation of a 980 nm near-IR laser, the observed UCL intensities for the BaYF 5 :Yb,Er,Bi x UCNPs display first an increasing trend and then a decreasing trend with an increase in the ratio x , giving a maximum at x = 2.5. A possible energy-transfer process and simplified energy levels of the BaYF 5 :Yb,Er,Bi x UCNPs were proposed. The potential of the BaYF 5 :Yb,Er,Bi x UCNPs as contrast agents for computerized tomography (CT) imaging was successfully demonstrated. An obvious accumulation of BaYF 5 :Yb,Er,Bi x in tumor sites was achieved because of high passive targeting by the enhanced permeability and retention effect and relatively low uptake by a reticuloendothelial system such as liver and spleen. This work paves a new route for the design of luminescence-enhanced UNCPs as promising bioimaging agents for cancer theranostics.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO 2.9 -WSe 2 -PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H 2 O 2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.

The radioresistance of tumor cells is considered to be an Achilles' heel of cancer radiotherapy. Thus, an effective and biosafe radiosensitizer is highly desired but hitherto remains a big challenge. With the rapid progress of nanomedicine, multifunctional inorganic nanoradiosensitizers offer a new route to overcome the radioresistance and enhance the efficacy of radiotherapy. Herein, poly(vinylpyrrolidone) (PVP)-modified Bi 2 WO 6 nanoplates with good biocompatibility were synthesized through a simple hydrothermal process and applied as a radiosensitizer for the enhancement of radiotherapy for the first time. On the one hand, the high- Z elements Bi ( Z = 83) and W ( Z = 74) endow PVP-Bi 2 WO 6 with better X-ray energy deposition performance and thus enhance radiation-induced DNA damages. On the other hand, Bi 2 WO 6 semiconductors exhibit significant photocurrent and photocatalytic-like radiocatalytic activity under X-ray irradiation, giving rise to the effective separation of electron/hole (e - /h + ) pairs and subsequently promoting the generation of cytotoxic reactive oxygen species, especially hydroxyl radicals ( • OH). The γ-H2AX and clonogenic assays demonstrated that PVP-Bi 2 WO 6 could efficiently increase cellular DNA damages and colony formations under X-ray irradiation. These versatile features endowed PVP-Bi 2 WO 6 nanoplates with enhanced radiotherapy efficacy in animal models. In addition, Bi 2 WO 6 nanoplates can also serve as good X-ray computed tomography imaging contrast agents. Our findings provide an alternative nanotechnology strategy for tumor radiosensitization through simultaneous radiation energy deposition and radiocatalysis.

The development of a new multifunctional nanomedicine capable of enhancing radiosensitization by photo-induced hyperthermia for the inhibition of cancer growth and metastasis is highly required for efficient treatment of cancer cells. Compared to the first near-infrared (NIR) window, the second NIR window light could provide a maximum penetration depth as well as minimizing autofluorescence due to its low scattering and energy absorption. Here, we report a new versatile theranostic agent based on ternary Cu3BiSe3 nanoparticles (NPs) modified by poly(vinylpyrollidone) (PVP-Cu3BiSe3). Benefiting from their preferable X-ray attenuation ability and strong NIR absorbance in the second NIR biological window, PVP-Cu3BiSe3 NPs can not only deposit more radiation doses to destroy the cancer cells, but also conduct the optical energy into hyperthermia for thermal eradication of tumor tissues and the improvement of the tumor oxygenation to overcome the hypoxia-associated radio-resistance of tumors. According to both in vitro and in vivo results, exposure to an X-ray plus 1064 nm laser completely kills cancer cells and even inhibits tumor metastasis, displaying no warning signs of a relapse. On the other hand, PVP-Cu3BiSe3 NPs can be used as a multi-model imaging agent for X-ray computer tomography (CT) and photoacoustic tomography (PAT) imaging. These demonstrate the potential of PVP-Cu3BiSe3 NPs in multimodal imaging-guided synergetic radiophotothermal therapy of deep-seated tumors and effective inhibition of their metastasis.

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 (MoS 2 -BNN6) is reported through the simple assembly of α-cyclodextrin-modified MoS 2 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 MoS 2 -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 MoS 2 -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 MoS 2 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 MoS 2 -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., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Abnormal H 2 O 2 and cholesterol levels are closely related to many diseases. This work reports a facile process for the synthesis of oxidized glutathione (GSSG)-modified MoS 2 nanosheets (MoS 2 -GSSG NSs). The biocompatible MoS 2 -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 MoS 2 . The high peroxidase-like activity of MoS 2 -GSSG NSs was applied as a robust nanoplatform for low-cost, rapid, and highly effective colorimetric detection of H 2 O 2 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 O 2 to generate H 2 O 2 , which oxidized TMB to generate a blue-colored product (oxTMB) under the catalysis of MoS 2 -GSSG NSs. The detection limit (DL) of total cholesterol and H 2 O 2 was as low as 5.36 and 0.51 μm, respectively. The linear ranges for detecting cholesterol and H 2 O 2 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., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

MoS 2 nanoflakes (MoS 2 NFs) with a diameter of ∼390 nm were obtained by a facile one-pot hydrothermal method and the NFs exhibited intrinsic peroxidase-like activity. After being modified by commonly used biocompatible surfactants including polyethyleneimine (PEI), polyacrylic acid (PAA), polyvinylpyrrolidone (PVP), and cysteine (Cys), the peroxidase-like catalytic activities of MoS 2 NFs were investigated by using 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS) as chromogenic substrates. Compared to the polymer modified MoS 2 NFs, Cys functionalized MoS 2 NFs exhibited a high catalytic activity toward H 2 O 2 in the presence of TMB or ABTS. Zeta potential and Michaelis-Menten analyses implied that the electrostatic force induced affinity or repulsion between the MoS 2 NFs and substrates, as well as surface modifications of the MoS 2 NFs played a key role in the catalytic reactions. Notably, a new peroxidase-like catalytic reaction mechanism was proposed based on the formation of a transient state of Cys-MoS 2 NFs containing H 2 O 2 and ABTS, and the catalytic reaction could occur because the Cys on the surface of the MoS 2 NFs served as an electron transfer bridge between H 2 O 2 and ABTS. Based on this finding, we also established a platform for colorimetric detection of H 2 O 2 and glucose using Cys-MoS 2 NFs as a peroxidase substitution. The limit of detection (LOD) was determined to be 4.103 μmol L -1 for H 2 O 2 , and the linear range (LR) was from 0 to 0.3 mmol L -1 . The LOD for glucose was 33.51 μmol L -1 and the LR was from 0.05 to 1 mmol L -1 , which is suitable for biomedical diagnosis. This work provides a new insight into the catalytic mechanism of peroxidase-like MoS 2 NFs, and paves the way for enzyme-like nanomaterials to be used for medical diagnosis.