Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy.

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

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.

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.

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.

Liquid-Phase Exfoliation and Functionalization of MoS2 Nanosheets for Effective Antibacterial Application.

A lysozyme (Lys)-assisted liquid-phase exfoliation technique was designed to synthesize MoS2 nanosheets (MoS2 -Lys NSs). As a novel nanozyme antibacterial agent with high peroxidase-like catalyst activity, MoS2 -Lys NSs showed good antibacterial efficacy against both Gram-negative ampicillin-resistant Escherichia coli (Ampr E. coli) and Gram-positive Bacillus subtilis. A possible antibacterial mechanism is also proposed. This work provides an effective antibacterial strategy based on the MoS2 -Lys NSs antibacterial agent.

Bi3+-Doped BaYF5:Yb,Er Upconversion Nanoparticles with Enhanced Luminescence and Application Case for X-ray Computed Tomography Imaging.

In this work, BaYF5:20%Yb3+/2%Er3+/x%Bi3+ (abbreviated as BaYF5:Yb,Er,Bix, where x = 0-3.0) upconversion nanoparticles (UCNPs) with various doping concentrations of Bi3+ were synthesized through a simple hydrothermal method. The influence of the doping amount of Bi3+ on the microstructures and upconversion luminescence (UCL) properties of the BaYF5:Yb,Er,Bix UCNPs was studied in detail. The doping concentration of Bi3+ 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 BaYF5:Yb,Er,Bix 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 BaYF5:Yb,Er,Bix UCNPs were proposed. The potential of the BaYF5:Yb,Er,Bix UCNPs as contrast agents for computerized tomography (CT) imaging was successfully demonstrated. An obvious accumulation of BaYF5:Yb,Er,Bix 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.

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.

Study on myocardial toxicity induced by lead halide perovskites nanoparticles.

Lead halide perovskites (LHPs) are outstanding candidates for next-generation optoelectronic materials, with considerable prospects of use and commercial value. However, knowledge about their toxicity is scarce, which may limit their commercialization. Here, for the first time, we studied the cardiotoxicity and molecular mechanisms of representative CsPbBr3 nanoparticles in LHPs. After their intranasal administration to Institute of Cancer Research (ICR) mice, using advanced synchrotron radiation, mass spectrometry, and ultrasound imaging, we revealed that CsPbBr3 nanoparticles can severely affect cardiac systolic function by accumulating in the myocardial tissue. RNA sequencing and Western blotting demonstrated that CsPbBr3 nanoparticles induced excessive oxidative stress in cardiomyocytes, thereby provoking endoplasmic reticulum stress, disturbing calcium homeostasis, and ultimately leading to apoptosis. Our findings highlight the cardiotoxic effects of LHPs and provide crucial toxicological data for the product.

Lung Toxicity and Molecular Mechanisms of Lead-Based Perovskite Nanoparticles in the Respiratory System.

Lead-based perovskite nanoparticles (Pb-PNPs) have found extensive applications across diverse fields. However, because of poor stability and relatively strong water solubility, the potential toxicity of Pb-PNPs released into the environment during their manufacture, usage, and disposal has attracted significant attention. Inhalation is a primary route through which human exposure to Pb-PNPs occurs. Herein, the toxic effects and underlying molecular mechanisms of Pb-PNPs in the respiratory system are investigated. The in vitro cytotoxicity of CsPbBr3 nanoparticles in BEAS-2B cells is studied using multiple bioassays and electron microscopy. CsPbBr3 nanoparticles of different concentrations induce excessive oxidative stress and cell apoptosis. Furthermore, CsPbBr3 nanoparticles specifically recruit the TGF-ß1, which subsequently induces epithelial-mesenchymal transition. In addition, the biodistribution and lung toxicity of representative CsPbBr3 nanoparticles in ICR mice are investigated following intranasal administration. These findings indicate that CsPbBr3 nanoparticles significantly induce pulmonary inflammation and epithelial-mesenchymal transition and can even lead to pulmonary fibrosis in mouse models. Above findings expose the adverse effects and molecular mechanisms of Pb-PNPs in the lung, which broadens the safety data of Pb-PNPs.

Ag-Activated Metal-Organic Framework with Peroxidase-like Activity Synergistic Ag+ Release for Safe Bacterial Eradication and Wound Healing.

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.

Ultrathin, Transparent, and High Density Perovskite Scintillator Film for High Resolution X-Ray Microscopic Imaging.

Inorganic perovskite quantum dots CsPbX3 (X = Cl, Br, and I) has recently received extensive attention as a new promising class of X-ray scintillators. However, relatively low light yield (LY) of CsPbX3 and strong optical scattering of the thick opaque scintillator film restrict their practical applications for high-resolution X-ray microscopic imaging. Here, the Ce3+ ion doped CsPbBr3 nanocrystals (NCs) with enhanced LY and stability are obtained and then the ultrathin (30 µm) and transparent scintillator films with high density are prepared by a suction filtration method. The small amount Ce3+ dopant greatly enhances the LY of CsPbBr3 NCs (about 33 000 photons per MeV), which is much higher than that of bare CsPbBr3 NCs. Moreover, the scintillator films made by these NCs with high density realize a high spatial resolution of 862 nm thanks to its thin and transparent feature, which is so far a record resolution for perovskite scintillator-based X-ray microscopic imaging. This strategy not only provides a simple way to increase the resolution down to nanoscale but also extends the application of as-prepared CsPbBr3 scintillator for high resolution X-ray microscopic imaging.

X-ray-facilitated redox cycling of nanozyme possessing peroxidase-mimicking activity for reactive oxygen species-enhanced cancer therapy.

Nanomaterials with shifting or mixed redox states is one of the most common studied nanozyme with peroxidase-like activity for chemodynamic therapy (CDT), which can decompose hydrogen peroxide (H2O2) of tumor microenvironment into highly toxic reactive oxygen species (ROS) by a nano-catalytic way. However, most of them exhibit an insufficient catalytic efficiency due to their dependence on catalytic condition. Herein, a potential methodology is proposed to enhance their enzymatic activity by accelerating the redox cycling of these nanomaterials with shifting or mixed redox states in the presence of X-ray. In this study, the nanocomposite consisting of SnS2 nanoplates and Fe3O4 quantum dots with shifting or mixed redox states (Fe2+/Fe3+) is used to explore the strategy. Under external X-ray irradiation, SnS2 cofactor as electron donor can be triggered to transfer electrons to Fe3O4, which promotes the regeneration of Fe2+ sites on the surface of the Fe3O4. Consequently, the regenerated Fe2+ sites react with the overexpressed H2O2 to persistently generate ROS for enhanced tumor therapy. The designed nanocomposite displays the synergistic effects of radiotherapy and CDT. The strategy provides a new avenue for the development of artificial nanozymes with shifting or mixed redox states in precise cancer treatments based on X-ray-enhanced enzymatic efficacy.

Two-dimensional nanomaterials beyond graphene for antibacterial applications: current progress and future perspectives.

The marked augment of drug-resistance to traditional antibiotics underlines the crying need for novel replaceable antibacterials. Research advances have revealed the considerable sterilization potential of two-dimension graphene-based nanomaterials. Subsequently, two-dimensional nanomaterials beyond graphene (2D NBG) as novel antibacterials have also demonstrated their power for disinfection due to their unique physicochemical properties and good biocompatibility. Therefore, the exploration of antibacterial mechanisms of 2D NBG is vital to manipulate antibacterials for future applications. Herein, we summarize the recent research progress of 2D NBG-based antibacterial agents, starting with a detailed introduction of the relevant antibacterial mechanisms, including direct contact destruction, oxidative stress, photo-induced antibacterial, control drug/metallic ions releasing, and the multi-mode synergistic antibacterial. Then, the effect of the physicochemical properties of 2D NBG on their antibacterial activities is also discussed. Additionally, a summary of the different kinds of 2D NBG is given, such as transition-metal dichalcogenides/oxides, metal-based compounds, nitride-based nanomaterials, black phosphorus, transition metal carbides, and nitrides. Finally, we rationally analyze the current challenges and new perspectives for future study of more effective antibacterial agents. This review not only can help researchers grasp the current status of 2D NBG antibacterials, but also may catalyze breakthroughs in this fast-growing field.

Stimuli-Responsive Small-on-Large Nanoradiosensitizer for Enhanced Tumor Penetration and Radiotherapy Sensitization.

Development of an efficient nanoradiosensitization system that enhances the radiation doses in cancer cells to sensitize radiotherapy (RT) while sparing normal tissues is highly desirable. Here, we construct a tumor microenvironment (TME)-responsive disassembled small-on-large molybdenum disulfide/hafnium dioxide (MoS2/HfO2) dextran (M/H-D) nanoradiosensitizer. The M/H-D can degrade and release the HfO2 nanoparticles (NPs) in TME to enhance tumor penetration of the HfO2 NPs upon near-infrared (NIR) exposure, which can solve the bottleneck of insufficient internalization of the HfO2 NPs. Simultaneously, the NIR photothermal therapy increased peroxidase-like catalytic efficiency of the M/H-D nanoradiosensitizer in TME, which selectively catalyzed intratumorally overexpressed H2O2 into highly oxidized hydroxyl radicals (·OH). The heat induced by PTT also relieved the intratumoral hypoxia to sensitize RT. Consequently, this TME-responsive precise nanoradiosensitization achieved improved irradiation effectiveness, potent oxygenation in tumor, and efficient suppression to tumor, which can be real-time monitored by computed tomography and photoacoustic imaging.

A two-step gas/liquid strategy for the production of N-doped defect-rich transition metal dichalcogenide nanosheets and their antibacterial applications.

Herein, we developed a general two-step gas expansion and exfoliation strategy based on a urea-assisted hydrothermal process combined with sonication exfoliation for the production of nitrogen (N)-doped plus defect-rich transition metal dichalcogenide (TMD) nanosheets (NSs) such as N-MoS2 and N-WS2 NSs. The interlayers of bulk MoS2 (or WS2) were expanded with urea molecules dissolved in distilled water, which were decomposed to NH3 during the hydrothermal process. Simultaneously, sulfur atoms were partly replaced by N atoms to achieve N doping. Subsequently, sonication exfoliation of the urea-treated bulk MoS2 (or WS2) promoted the production of defect-rich NSs. Importantly, the defect-rich N-MoS2 and N-WS2 NSs exhibit enhanced peroxidase-like catalytic activity after being captured by bacteria, and can catalyze hydrogen peroxide (H2O2) to produce more toxic hydroxyl radicals (˙OH) than non-N-doped MoS2 or WS2 NSs. As a result, the N-MoS2 or N-WS2 NSs were capable of effectively killing Gram-negative ampicillin resistant Escherichia coli (AmprE. coli) and Gram-positive endospore-forming Bacillus subtilis (B. subtilis) and promoting bacteria-infected wound healing. This work not only provides a simple, universal exfoliation strategy for producing defect-rich N-doped TMD NSs but also provides a promising catalytic antibacterial option and has potential for many other catalytic applications.

A Heterojunction Structured WO2.9-WSe2 Nanoradiosensitizer Increases Local Tumor Ablation and Checkpoint Blockade Immunotherapy upon Low Radiation Dose.

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 WO2.9-WSe2-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 H2O2 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.

Graphdiyne nanoradioprotector with efficient free radical scavenging ability for mitigating radiation-induced gastrointestinal tract damage.

X-ray irradiation-induced toxicity to gastrointestinal tract become a significant clinical problem when using radiotherapy for treating abdominal tumors neighbored to gastrointestinal tissue, which not only often prevents these tumors from receiving a definitive therapeutic dose but also causes a series of gastrointestinal diseases, such as anorexia, abdominal pain, diarrhea and hematochezia. And thus it seriously reduces the therapeutic outcome and life quality of patients. Therefore, the development of gastrointestinal radioprotectors is essential. However, the commercial gastrointestinal radioprotectors in clinical are still rare. In view of this, we prepared bovine serum albumin (BSA) modified graphdiyne (GDY) nanoparticles (GDY-BSA NPs) and for the first time studied its gastrointestinal radioprotection ability. The unique advantages of GDY nanomaterial, including high free radical scavenging ability, good chemical stability in gastric acid condition, relatively longer residence time in gastrointestinal tract and good biosafety under oral administration, provide the favorable prerequisites for it to be used as the gastrointestinal radioprotector. In vitro experimental results indicated that the GDY-BSA NPs powerfully reduced DNA damage and improved viability of the irradiated gastrointestinal cells. In vivo results showed that the GDY-BSA NPs significantly decrease radiation-induced diarrhea, weight loss, and gastrointestinal tissue pathological damage of mice. Furthermore, we also deeply studied the gastrointestinal radioprotective mechanism of GDY-BSA NPs, which indicated that the GDY-BSA NPs effectively inhibited reactive oxygen species (ROS)-induced apoptosis signal pathway, and thus reduced gastrointestinal cell apoptosis. Our work for the first time employed BSA-GDY NPs to mitigating radiation-induced gastrointestinal tract damage, which not only promotes the exploration of new gastrointestinal tract radioprotectors, but also is the good guidance for the treatment of gastrointestinal diseases by nano-drug.

Bi2WO6 Semiconductor Nanoplates for Tumor Radiosensitization through High- Z Effects and Radiocatalysis.

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 Bi2WO6 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-Bi2WO6 with better X-ray energy deposition performance and thus enhance radiation-induced DNA damages. On the other hand, Bi2WO6 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-Bi2WO6 could efficiently increase cellular DNA damages and colony formations under X-ray irradiation. These versatile features endowed PVP-Bi2WO6 nanoplates with enhanced radiotherapy efficacy in animal models. In addition, Bi2WO6 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.

Enhanced radiosensitization of ternary Cu3BiSe3 nanoparticles by photo-induced hyperthermia in the second near-infrared biological window.

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.