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Lateral furan-expansion of polycyclic aromatics, which enables multiple O-doping and peripheral edge evolution of rylenes, is developed for the first time. Tetrafuranylperylene TPF-4CN and octafuranylquaterrylene OFQ-8CN were prepared as model compounds bearing unique fjord edge topology and helical conformations. Compared to TPF-4CN, the higher congener OFQ-8CN displays a largely red-shifted (≈333â nm) and intensified absorption band (λmax =829â nm) as well as a narrowed electrochemical band gap (≈1.08â eV) due to its pronounced π-delocalization and emerging of open-shell diradicaloid upon the increase of fjord edge length. Moreover, strong circular dichroism signals in a broad range until 900â nm are observed for open-shell chiral OFQ-8CN, owing to the excellent conformational stability of its central bis(tetraoxa[5]helicene) fragments. Our studies provide insights into the relationships between edge topologies and (chir)optoelectronic properties for this novel type of O-doped PAHs.
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Here we report stepwise solution-synthesis of linear nonalternant nanoribbons (NNRs), featuring pentagonal rings peri-fused onto the repeating perylene unit. The X-ray single-crystal structures demonstrated their π-backbones as a twisted ribbon, with the longest crystalline length of the nanoribbon up to 3.9â nm. NNRs exhibited an orange to deep-red photoluminescence even under the room light, with absolute ΦF up to 82 %, most likely due to ring-strain induced molecular stiffness. Benefiting from the enlarged size and the antiaromatic character of pentagons, all of NNRs possessed ambipolar redox properties, especially for longer nanoribbons showing multiple reversible reductions and oxidations. In addition, experimental and theoretical results indicated a ground state open-shell singlet diradicaloid for the dication of longer NNRs. Our studies reveal the intriguing nonalternant structures and physical properties of this type of nanoribbons, involving the striking effects of the multiple annulated pentagons, and also provide fundamental insights into their electronic structures.
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During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.
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Núcleo Celular/metabolismo , Eritroblastos/metabolismo , Eritropoese/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas Nucleares/metabolismo , Apoptose/fisiologia , Caspase 3/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Citoplasma/metabolismo , Regulação da Expressão Gênica/fisiologia , Doenças Hematológicas/metabolismo , HumanosRESUMO
A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, ß-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the µM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.
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Corantes Fluorescentes/química , Fluoretos/química , Agentes Neurotóxicos/química , Compostos de Sulfidrila/química , Enxofre/química , Concentração de Íons de HidrogênioRESUMO
Aim to classify typical hot springs in Guizhou, China and their relevance to health. Assessing geochemical characters of typical hot springs of Guizhou and classifying through hierarchical cluster analysis, an epidemiologic study was conducted to analyze the correlation between hot spring types and health, which showed typical hot springs in Guizhou can be divided into two types, A and B. Type A is rich in fluorine, metasilicic acid, radon components and a large number of essential elements, such as Na, that the human body needs, with trace elements, such as Cr and V, that are essential or possibly essential. Type B is rich in fluorine, metasilicate, strontium components and a large number of essential elements, Ca, Mg, and S, with trace elements, Cu, Mn, Mo, Co, and Ni, that are essential or possibly essential. These hot springs' effects on the health of those bathing in them showed both types were associated with bone and joint diseases. Having bathed in hot springs during the past year was associated with skin symptoms and bone and joint symptoms, and having bathed within the past two weeks was linked to sleep quality and levels of appetite and energy. However, differences do exist between the correlation between the two types and some chronic diseases, with Type A hot springs significantly related to cardiovascular and cerebrovascular diseases and diabetes and Type B to hypertension. This classification of Guizhou's hot springs can guide the future development and use of hot spring physiotherapy.
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Promoção da Saúde/métodos , Fontes Termais , Oligoelementos/análise , Água/química , China , HumanosRESUMO
The design of highly efficient drug carriers, and the development of appropriate techniques to monitor their mechanism of action and therapeutic effect, are both critical for improving chemotherapy. Herein, a polymeric nanoparticle, PAH-Cit/DOX (poly(allylamine)-citraconic anhydride/doxorubicin), was synthesized and used as a nanodrug system for the efficient delivery and pH-responsive release of doxorubicin (DOX) into cancer cells. The PAH-Cit/DOX nanoparticles were stable at physiological pH but effectively released DOX under weakly acidic conditions. The release efficiency was 90.6% after 60 h of dialysis in phosphate-buffered saline at pH 5.5. Confocal images showed the rapid movement of the drug from the cytoplasm to the nucleus, indicating the effective drug release MCF-7 cells. Notably, the combination of fluorescence lifetime imaging microscopy (FLIM) and phasor analysis (phasor-FLIM) provides an approach to monitor the dynamic change of DOX fluorescence lifetime in intercellular environments. Phasor-differentiated lifetime pixel intensity in FLIM images was quantified and used to evaluate the DOX release from nanocarriers, making it possible to detect the dynamics of intracellular release and transport of DOX.
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Antibióticos Antineoplásicos/farmacologia , Anidridos Citracônicos/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Poliaminas/química , Polímeros/química , Polipropilenos/química , Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Microscopia Confocal , Microscopia de Fluorescência , Nanopartículas/toxicidade , Polímeros/síntese química , Polímeros/toxicidade , Polipropilenos/síntese química , Polipropilenos/toxicidadeRESUMO
Herein, fluorescence lifetime imaging microscopy (FLIM) was used to directly measure eosin fluorescence lifetimes from H&E-stained umbilical artery, and a further utilization of eosin for high-content and multi-target analysis was proposed for the first time. Smooth muscles, collagens, and elastic fibers can be distinguished by eosin fluorescence lifetimes (P < 0.001). Erythrocytes, smooth muscles, elastic fibers, and type I and III collagen from the H&E-stained umbilical artery can be simultaneously identified by multiplexed fluorescence lifetimes of eosin. Use of eosin and lifetime-based separation is a potential method to simplify the special staining for clinicopathologic examination. Multiplexed eosin fluorescence lifetimes may be a newly developed method that can directly determine the relative content of elastic fiber and collagens from the H&E-stained sections. FLIM may have potential applications as an assisted tool in the assessment of the severity and complexity of cardiovascular diseases.
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Vasos Sanguíneos/diagnóstico por imagem , Amarelo de Eosina-(YS) , Microscopia de Fluorescência , Coloração e Rotulagem , HumanosRESUMO
The aim of this study was to distinguish basal cell carcinoma (BCC) from actinic keratosis (AK) and Bowen's disease (BD) by fluorescence lifetimes of hematoxylin and eosin (H&E) and phasor analysis. Pseudocolor images of average fluorescence lifetime (τm) exhibited more contrast than conventional bright field and/or fluorescence images of H&E-stained sections. The mean values (µ) of τm distribution (τmµ) in three layers of skin were first explored for comparison with the corresponding layers of AK, BD, and BCC. Moreover, analysis of the H&E fluorescence lifetimes in the phasor space was performed by observing clusters in specific regions of the phasor plot. Various structures in the skin were distinguished. Comparisons of phase distributions from the corresponding layers of skin resulted in quantitative separation and calculation of distinctive parameters including coordinate values, diagonal slopes, and phasor areas. The combination of fluorescence lifetime imaging microscopy (FLIM) and phasor approach (phasor-FLIM) provides a simple method for histopathology analysis and can significantly improve the accuracy of bright field H&E diagnosis. We therefore believe that phasor-FLIM is an aided tool with the potential to provide rapid confirmation of diagnostic criteria and classification of histological types of skin neoplasms.
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Doença de Bowen/diagnóstico , Carcinoma Basocelular/diagnóstico , Ceratose Actínica/diagnóstico , Microscopia de Fluorescência/métodos , Neoplasias Cutâneas/diagnóstico , Área Sob a Curva , Doença de Bowen/patologia , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Humanos , Ceratose Actínica/patologia , Curva ROC , Neoplasias Cutâneas/patologiaRESUMO
The phasor approach to fluorescence lifetime imaging microscopy (FLIM) is used to identify different types of tissues from hematoxylin and eosin (H&E) stained basal cell carcinoma (BCC) sections. The results suggest that working directly on the phasor space with the clustering assignment achieves immunofluorescence like simultaneous five or six-color imaging by using multiplexed fluorescence lifetimes of H&E. The phase approach is of particular effectiveness for enhanced visualization of the abnormal morphology of a suspected nidus. Moreover, the phasor approach to H&E FLIM data can determine the actual paths or the infiltrating trajectories of basophils and immune cells associated with the preneoplastic or neoplastic skin lesions. The integration of the phasor approach with routine histology proved its available value for skin cancer prevention and early detection. We therefore believe that the phasor analysis of H&E tissue sections is an enhanced visualization tool with the potential to simplify the preparation process of special staining and serve as color contrast aided imaging in clinical pathological examination.
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Carcinoma Basocelular/diagnóstico por imagem , Amarelo de Eosina-(YS)/química , Hematoxilina/química , Imagem Óptica/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Carcinoma Basocelular/patologia , Humanos , Microscopia de Fluorescência , Neoplasias Cutâneas/patologia , Coloração e RotulagemRESUMO
Metallic glass film of Pr60Al10Ni10Cu20 is proposed to be used as a resist of phase-change lithography (PCL). PCL is a mask-less lithography technology by using laser-direct-writing to create the intended nanopatterns. Thermal distribution in the PrAlNiCu film after exposure is calculated by finite element method (FEM). Thin films are exposed by continuous-wave laser and selective etched by nitric-acid solution, and the patterns are discerned by optical and atomic force microscope. The etching rate of as-deposited PrAlNiCu is thus nearly five times of the crystalline film. These results indicate that PrAlNiCu metallic glass film is a promising resist for phase-change lithography.
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Ischemia and reperfusion (IR) injury constitutes a pivotal mechanism of tissue damage in pathological conditions such as stroke, myocardial infarction, vascular surgery, and organ transplant. Imaging or monitoring of the change of an organ at a molecular level in real time during IR is essential to improve our understanding of the underlying pathophysiology and to guide therapeutic strategies. Herein, we report molecular imaging of a rat model of hepatic IR with the autofluorescence of mitochondrial flavins. We demonstrate a revelation of the histological characteristics of a liver in vivo with no exogenous stain and show that intravital autofluorescent images exhibited a distinctive spatiotemporal variation during IR. The autofluorescence decayed rapidly from the baseline immediately after 20-min ischemia (approximately 30% decrease in 5 min) but recovered gradually during reperfusion (to approximately 99% of the baseline 9 min after the onset of reperfusion). The autofluorescent images acquired during reperfusion correlated strongly with the reperfused blood flow. We show further that the autofluorescence was produced predominantly from mitochondria, and the distinctive autofluorescent variation during IR was mechanically linked to the altered balance between the flavins in the oxidized and reduced forms residing in the mitochondrial electron-transport chain. Our approach opens an unprecedented route to interrogate the deoxygenation and reoxygenation of mitochondria, the machinery central to the pathophysiology of IR injury, with great molecular specificity and spatiotemporal resolution and can be prospectively translated into a medical device capable of molecular imaging. We envisage that the realization thereof should shed new light on clinical diagnostics and therapeutic interventions targeting IR injuries of not only the liver but also other vital organs including the brain and heart.
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Mitocôndrias Hepáticas/patologia , Imagem Molecular/métodos , Traumatismo por Reperfusão/patologia , Animais , Fluorescência , Hepatócitos/patologia , Fígado/patologia , Masculino , Camundongos , Ratos , Ratos WistarRESUMO
Rational design and preparation of high-performance bifunctional oxygen electrocatalysts with effective sites and excellent mass/electron transfer structures are in demand for Zn-air batteries to overcome the sluggish oxygen reduction/evolution kinetics. Herein, a scalable and facile strategy is proposed to obtain brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon catalysts with optimized active sites and hierarchical nanostructures. Systematic investigation indicates that nanoheterogeneous interfaces with appropriate composition deliver significantly improved electrochemical activity. As a result, a zinc-air battery assembled with the obtained Co/CoSe nanoheterostructures embedded in the N-doped carbon (CoSe/Co@NC-1) catalyst exhibits outstanding electrochemical performance with a peak power density of 215 mW cm-2 and excellent stability for 475 hours (2850 cycles). These results indicate that this strategy is an effective method for fabricating multicomponent and hierarchically nanostructured materials with enhanced catalytic efficiency for advanced energy devices.
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In situ monitoring multidrug release in complex cellular microenvironments is significant, and currently, it is still a great challenge. In this work, a smart nanocarrier with the capability of codelivery of small molecules and gene materials as well as with Förster resonance energy transfer (FRET)-modulated fluorescence lifetime is fabricated by integrating gold nanoparticles (the acceptor) into dual-mesoporous silica loaded with multiple drugs (the donor). Once internalized into tumor cells, in weakly acidic environments, the conformation switch of the polymer grafted on nanocarriers causes its shedding from the mesopores, triggering the release of drugs. Simultaneously, based on the strong overlap between the emission spectrum of donors and the absorption spectrum of the acceptors, any slight fluctuation of the dissociation of the drugs from nanocarriers can result in a change in the FRET-modulated lifetime signal due to the extraordinarily sensitive FRET signal to the separation distance between donors and acceptors. All these implied the potential applications of this nanoplatform in various biomedical fields that require the codelivery and real-time monitoring of multidrug-based synergistic therapy.
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Transferência Ressonante de Energia de Fluorescência , Nanopartículas Metálicas , Ouro , Nanopartículas Metálicas/uso terapêutico , Microambiente Celular , PolímerosRESUMO
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes. The condition is typically marked by pruritus (itching) and elevated levels of liver enzymes and bile acids. The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate, but the efficacy of this approach remains less than optimal. Recently, polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects. AIM: To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ ademetionine 1,4-butanedisulfonate on bile acid levels, liver enzyme indices, and pregnancy outcomes in patients with ICP. METHODS: From June 2020 to June 2021, 600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via random-number table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (control group, n = 300) or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (combined group, n = 300). Outcome measures included bile acids levels, liver enzyme indices, and pregnancy outcomes. RESULTS: Prior to treatment, no significant differences were observed between the two groups (P > 0.05). Post-treatment, patients in both groups had significantly lower pruritus scores, but the triple-drug combination group had lower scores than the dual-drug combination group (P < 0.05). The bile acid levels decreased significantly in both groups, but the decrease was more significant in the triple-drug group (P < 0.05). The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group (P < 0.05). CONCLUSION: Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP, providing a positive impact on pregnancy outcome and a high safety profile. Further clinical trials are required prior to clinical application.
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Although the honey produced by Lespedeza bicolor Turcz. is precious because of its medicinal value, its pharmacological mechanism is still unclear. Here, its anti-inflammatory and antioxidant functions on lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages were analyzed using targeted and non-targeted metabolomics. Results showed that twelve polyphenols were identified in L. bicolor honey using UHPLC-QQQ-MS/MS. L. bicolor honey extract could scavenge the free radicals DPPH⢠and ABTS+ and reduce Fe3+. Furthermore, pretreatment with L. bicolor honey extract significantly decreased NO production; suppressed the expression of COX-2, IL-10, TNF-α, and iNOS; and upregulated HO-1's expression in the cells with LPS application. UHPLC-Q-TOF-MS/MS-based metabolomics results revealed that L. bicolor honey extract could protect against inflammatory damage caused by LPS through the reduced activation of sphingolipid metabolism and necroptosis pathways. These findings demonstrate that L. bicolor honey possesses excellent antioxidant and anti-inflammatory activities.
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A scalable and facile solid-catalyzed growth approach is reported to integrate N-doped carbon tentacles with metal selenide nanoparticles, showing great potential for mass production of non-precious metal catalysts for rechargeable Zn-air batteries.
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BACKGROUND: In recent years, inductively coupled plasma mass spectrometry (ICP-MS) has been widely used in the field of molecular biology because of its unique advantages. Anthrax is a widespread and long-standing infectious disease, which affects and restricts people's work and life seriously. OBJECTIVE: The study goal is to develop a new method for the detection of anthrax. METHODS: A rapid, sensitive and accurate method for the detection of anthrax characteristic DNA was proposed by combing gold nanoparticles (AuNPs) and inductively coupled plasma mass spectrometry. RESULTS: The linear range of this method is 100-2500 pmol/L and the limit of detection of 16.61 pmol/L. CONCLUSION: The proposed method has numerous advantages, including simplicity of operation, high sensitivity, and specificity, which provides a new idea for the detection of anthrax. Importantly, this methodology has good potential for the detection of other biological substances such as bacteria and viruses by changing the modification sequence on the nanoparticle probe.
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Antraz , Nanopartículas Metálicas , Humanos , Ouro/química , Espectrometria de Massas/métodos , Nanopartículas Metálicas/química , Antraz/diagnóstico , DNA/análise , DNA/química , DNA/genéticaRESUMO
Honey produced from Lespedeza bicolor Turcz. (L. bicolor) is highly valued and relatively rare, leading to adulterated or ersatz substitutes in the marketplace, with no reliable authentication methods available for enforcement of regulations. Here, we characterize the physicochemical parameters (water content, pH, sugar content, amylase activity, and 5-hydroxymethylfurfural content) in L. bicolor honey and palynological characteristics of L. bicolor pollen as reference for assessment of quality and monoflorality. Mass spectrometry with Orthogonal Partial Least Square Discriminant Analysis of chemical constituent data from L. bicolor, chaste, acacia, jujube, and linden honeys, all commonly sold in China, identified kaempferol-3-O-galactoside as a candidate chemical marker of L. bicolor honey. We validated this screening method and quantified kaempferol-3-O-galactoside in L. bicolor, but not other honeys, at concentrations between 90.2 and 430.1 µg/kg, with high sensitivity (LOD = 0.002 mg/kg), linearity (R2 ≥ 0.99), and recovery (90.2%-110.6%), supporting its use in authenticating L. bicolor honey.
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Mel , Lespedeza , Galactosídeos , Mel/análise , QuempferóisRESUMO
Indocyanine green-loaded mesoporous silica-coated gold nanorods (ICG-loaded Au@SiO2) were prepared for the dual capability of X-ray computed tomography (CT) and fluorescence imaging. X-ray CT scanning showed that ICG-loaded Au@SiO2 could provide significant contrast enhancement; Near-infrared fluorescence generated by the nanomaterial was present up to 12 h post intratumoral injection, thus enabling ICG-loaded Au@SiO2 to be used as a promising dual mode imaging contrast agent. Multiplexed images can be more easily obtained with this novel type of multimodal nanostructure compared with traditional contrast agents. The dual mode imaging probe has great potential for use in applications such as cancer targeting, molecular imaging in combination with radiotherapy, and photothermolysis.
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Meios de Contraste , Verde de Indocianina , Nanopartículas Metálicas , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Linhagem Celular Tumoral , Diagnóstico por Imagem/métodos , Feminino , Fluorescência , Corantes Fluorescentes , Ouro , Camundongos , Camundongos Nus , Nanocompostos , Nanotubos , Dióxido de Silício , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/diagnóstico por imagemRESUMO
We explored the biocompatible gold nanoparticles (GNPs) with surface modified by chitosan in the applications of cell's response to X-ray irradiation. Substantial amounts of chitosan modified gold nanoparticles (CS-GNPs) were found to be internalized in cell cytoplasm revealed by transmission electron microscopy. Their in vitro cytotoxicity effects on MGC-803 cells and GES-1 cells were observed at 24, 48 and 72 h. The MTT results showed that CS-GNPs own excellent biocompatibility. The dose enhancement based on CS-GNPs induced the damage of MGC-803 cells under X-ray irradiation, monitored by clonogenic cell survival assay. We also investigated their effects on the survival rates of MGC-803 cells during irradiation for a dose up to 10 Gy using a radio-oncology linear accelerator (6 MeV). The survival fraction of cells incubated with different concentration of CS-GNPs was obviously reduced in comparison with that irradiation alone. The result also revealed an increase of cell inhibition with increasing the concentration of CS-GNPs. In conclusion, CS-GNPs can enhance the cell radiation therapeutic sensitivity, and have potential application in tumor irradiation therapy in near future.