tellurium and Carcinoma--Hepatocellular

Topics: alpha-Fetoproteins; Biocatalysis; Biomarkers, Tumor; Cadmium Compounds; Carcinoma, Hepatocellular; Glypicans; Humans; Liver Neoplasms; Quantum Dots; Tellurium

Although nanoparticles based on Group 8 elements such as Fe and Ru have been developed, not much is known about Os nanoparticles. However, Os-based nanostructures might have potential in various applications including biomedical fields. Therefore, in this study, we synthesized Os-Te nanorods (OsTeNRs) by solvothermal galvanic replacement with Te nanotemplates. We explored the nanozymatic activity of the synthesized OsTeNRs and found that they exhibited superior photothermal conversion and photocatalytic activity. Along with chemotherapy (regorafenib) and immunotherapy, the nanozymatic, photothermal, and photodynamic activities of OsTeNRs were harnessed to develop a pentamodal treatment for hepatocellular carcinoma (HCC);

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Catalysis; Cell Line, Tumor; Drug Carriers; Liver Neoplasms; Male; Mice, Inbred C57BL; Nanotubes; Osmium; Phenylurea Compounds; Photochemotherapy; Pyridines; Tellurium; Xenograft Model Antitumor Assays

A method is described for the simultaneous determination of hepatocellular carcinoma-associated microRNA-122 and microRNA-199a/b-3p. This probe consists of two kinds of nanomaterials. The first comprises CdTe@CdS core-shell quantum dots which, on excitation at 375 nm give two emissions, with peak wavelengths at 543 (g-QDs) and at 627 nm (r-QDs). The second comprises gold nanoparticles acting as a quencher. In the absence of the target, g-QD-N1 and r-QD-N2 are stable due to the fluorescence stability. With the addition of microRNA-122 and microRNA-199a/b-3p, g-QD-N1 and r-QD-N2 are conjugated to the surface of AuNP-S1/S2 through base complementary pairing. As a result, fluorescence resonance energy transfer (FRET) occurs, resulting in a decrease at 550 nm and 635 nm respectively, which can realize the simultaneous detection of two different microRNAs. Detection is achieved within 50 min. The detection limits (3σ/k) are 0.2 nM for microRNA-122 and 0.5 nM for microRNA-199a/b-3p. The clinical applicability of the assay was demonstrated by detecting microRNAs in human serum and different cell lysates. Graphical abstractSchematic for the simultaneous determination of microRNA-122 and microRNA-199a/b-3p by FRET.

Topics: Biosensing Techniques; Cadmium Compounds; Carcinoma, Hepatocellular; Fluorescence Resonance Energy Transfer; Fluorometry; Humans; Limit of Detection; Liver Neoplasms; MicroRNAs; Neoplasms; Nucleic Acid Hybridization; Quantum Dots; Sulfides; Tellurium

Topics: Apoptosis; Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; DNA Damage; Glutathione; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Mutagens; Oxidative Stress; Quantum Dots; Reactive Oxygen Species; Tellurium

The mechanisms of toxicity related to human hepatocellular carcinoma HepG2 cell exposures to cadmium telluride quantum dots (CdTe-QDs) were investigated. CdTe-QDs caused cytotoxicity in HepG2 cells in a dose- and time-dependent manner. Treated cells showed an increase in reactive oxygen species (ROS). Altered antioxidant levels were demonstrated by depletion of reduced glutathione (GSH), a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and an increased NF-E2-related Factor 2 (Nrf2) activation. Enzyme assays showed that superoxide dismutase (SOD) activity was elevated whereas catalase (CAT) and glutathione-S-transferase (GST) activities were depressed. Further analyses revealed that CdTe-QD exposure resulted in apoptosis, indicated by changes in levels of caspase-3 activity, poly ADP-ribose polymerase (PARP) cleavage and phosphatidylserine externalization. Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure. Involvement of the intrinsic/mitochondrial apoptotic pathway was indicated by decreased levels of B-cell lymphoma 2 (Bcl2) protein and mitochondrial cytochrome c, and by increased levels of mitochondrial Bcl-2-associated X protein (Bax) and cytosolic cytochrome c. Further, mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (Erk1/2), and p38 were all activated. Our findings reveal that CdTe-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein kinases, leading to apoptosis via both extrinsic and intrinsic pathways. Since the effects of CdTe-QDs on selected biomarkers were similar or greater compared to those of CdCl2 at equivalent concentrations of cadmium, the study suggests that the toxicity of CdTe-QDs arises from a combination of the effects of cadmium and ROS generated from the NPs.

Topics: Apoptosis; Cadmium Compounds; Carcinoma, Hepatocellular; Catalase; Cell Survival; Cytochromes c; Glutathione; Glutathione Disulfide; Hep G2 Cells; Humans; Liver Neoplasms; Microscopy, Confocal; Mitogen-Activated Protein Kinases; NF-E2-Related Factor 2; Oxidative Stress; Quantum Dots; Signal Transduction; Superoxide Dismutase; Tellurium

Nanoconjugates composed of drug molecules encapsulated in quantum dots (QDs) attract enormous attention due to their promising bioimaging and biomedical applications. Here, the anticancer efficiency of potential pharmacophore agents (o-carborane (Cb), o-carborane-C-carboxylic acid (Cbac1), and o-carborane-C(1)C(2)-dicarboxylic acid (Cbac2) coupling with cadmium telluride QDs capped with cysteamine (CA-CdTe QDs)) have been explored. Compared with free CA-CdTe QDs, the composites consisting of Cbac1/Cbac2 and safe-dosage QDs can greatly improve the inhibition efficiency toward SMMC-7721 hepatocellular carcinoma cells with the aid of our real-time cell bioelectronic sensing system and the MTT assay. The enhanced cytotoxicity correlates with increased intracellular reactive oxygen species generation and cell apoptosis. Confocal laser scanning fluorescent microscopy shows improved cellular uptake and drug distribution of the Cbac1/Cbac2-CdTe QDs nanoconjugates. This work raises the possibility that the carborane pharmacophore in combination with QDs or other anticancer drugs may be viable for efficient cancer diagnosis and chemotherapy.

Topics: Apoptosis; Cadmium Compounds; Carboxylic Acids; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Humans; Nanostructures; Tellurium

The enzyme α-L-fucosidase (AFu) plays an important role in the diagnosis of hepatocellular carcinoma (HCC) and fucosidosis. In this paper, a simple, sensitive and precise method based upon measuring the fluorescence quenching of CdTe semiconductor quantum dots (QDs) was developed for detecting the enzymatic activity of AFu. The detection limit of AFu was 0.01 U/L (n = 3) and the linear relationship was 0.01-4 U/L. The selectivity experiment indicated excellent selectivity for AFu over a number of interfering species. We have also studied the detection mechanism of AFu by X-ray photoelectron spectroscopy (XPS) and found that the quenching effect was caused by the oxidation of tellurium by 2-chloro-4-nitrophenol (2-CNP) which produced in AFu catalytic reaction. Moreover, the AFu sensor based on QDs was used satisfactorily for the assessment of AFu activity in serum samples. It will most probably be applicable in assembling diagnostic microdevice to realize the rapid clinic analysis of AFu.

Topics: alpha-L-Fucosidase; Cadmium Compounds; Carcinoma, Hepatocellular; Fucosidosis; Humans; Limit of Detection; Liver Neoplasms; Quantum Dots; Spectrometry, Fluorescence; Tellurium

In this report, we describe the effect of conjugating o-carborane-C(1)C(2)-dicarboxylic acid (o-C2B10H10-C2O4H2, denoted as Cbac2) to cadmium telluride quantum dots (CdTe QDs) capped with cysteamine on the photophysics and cytotoxicity of the QDs. Cbac2 quenches the fluorescence intensity and induces a red shift of the fluorescence emission peak. Meanwhile, studies with a real time cell electronic sensing (RT-CES) system and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay indicate that the combination of the carborane carboxylic acid derivative Cbac2 with relevant QDs can efficiently improve the inhibition efficiency for target cancer cells when compared with a single ligand or the CdTe QDs alone. This study raises the possibility for the labeling of the important pharmacophore with QDs and the design of new promising anticancer agents containing the carborane pharmacophores for cancer therapy.

Topics: Boranes; Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Color; Humans; Lighting; Microscopy, Fluorescence; Nanocapsules; Quantum Dots; Tellurium

Data regarding tellurium (Te) toxicity are scarce. Studies on its metabolism, performed mainly in bacteria, underline a major role of reactive oxygen species (ROS). We investigated whether tellurite undergoes redox cycling leading to ROS formation and cancer cell death. The murine hepatocarcinoma Transplantable Liver Tumor (TLT) cells were challenged with tellurite either in the presence or in the absence of different compounds as N-acetylcysteine (NAC), 3-methyladenine, BAPTA-AM, and catalase. NAC inhibition of tellurite-mediated toxicity suggested a major role of oxidative stress. Tellurite also decreased both glutathione (GSH) and ATP content by 57 and 80%, respectively. In the presence of NAC however, the levels of such markers were almost fully restored. Tellurite-mediated ROS generation was assessed both by using the fluorescent, oxidation-sensitive probe dichlorodihydrofluorescein diacetate (DCHF-DA) and electron spin resonance (ESR) spectroscopy to detect hydroxyl radical formation. Cell death occurs by a caspase-independent mechanism, as shown by the lack of caspase-3 activity and no cleavage of poly(ADP-ribose)polymerase (PARP). The presence of gamma-H2AX suggests tellurite-induced DNA strand breaking, NAC being unable to counteract it. Although the calcium chelator BAPTA-AM did show no effect, the rapid phosphorylation of eIF2alpha suggests that, in addition to oxidative stress, an endoplasmic reticulum (ER) stress may be involved in the mechanisms leading to cell death by tellurite.

Topics: Adenosine Triphosphate; Animals; Carcinoma, Hepatocellular; Caspase 3; Cell Death; Cell Line, Tumor; Glutathione; Humans; Liver Neoplasms; Mice; Oxidative Stress; Reactive Oxygen Species; Tellurium

In this work we report on the development of novel hybrid material with enhanced photodynamic properties based on methylene blue and CdTe nanocrystals. Absorption spectroscopy, visible photoluminescence spectroscopy and fluorescence lifetime imaging of this system reveal efficient charge transfer between nanocrystals and the methylene blue dye. Near infra-red photoluminescence measurements provide evidence for an increased efficiency of singlet oxygen production by the methylene blue dye. In vitro studies on the growth of HepG2 and HeLa cancerous cells were also performed, they point towards an improvement in the cell kill efficiency for the methylene blue-semiconductor nanocrystals hybrid system.

Topics: Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Crystallization; HeLa Cells; Humans; Macromolecular Substances; Materials Testing; Methylene Blue; Molecular Conformation; Nanomedicine; Nanostructures; Particle Size; Photochemotherapy; Photosensitizing Agents; Quantum Dots; Semiconductors; Tellurium

We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

Topics: alpha-Fetoproteins; Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Chromatography, High Pressure Liquid; Diagnostic Imaging; Fluorescein-5-isothiocyanate; Humans; Immunoassay; Liver Neoplasms; Microscopy, Fluorescence; Quantum Dots; Spectrophotometry, Ultraviolet; Sulfides; Tellurium; Zinc Compounds

To effectively image living cells with quantum dots (QDs), particularly for those cells containing high content of native fluorophores, the two-photon excitation (TPE) with a femto-second 800 nm laser was employed and compared with the single-photon excitations (SPE) of 405 nm and 488 nm in BY-2 Tobacco (BY-2-T) and human hepatocellular carcinoma (QGY) cells, respectively. The 405 nm SPE produced the bright photoluminescence (PL) signals of cellular QDs but also induced a strong autofluorescence(AF) from the native fluorophores like flavins in cells. The AF occupied about 30% and 13% of the total signals detected in QD imaging channel in the BY-2-T and QGY cells, respectively. With the excitation of 488 nm SPE, the PL signals were lower than those excited with the 405 nm SPE, although the AF signals were also reduced. The 800 nm TPE generated the best PL images of intracellular QDs with the highest signal ratio of PL to AF, because the two-photon absorption cross section of QDs is much higher than that of the native fluorophores. By means of the TPE, the reliable cellular imaging with QDs, even for the cells having the high AF background, can be achieved.

Topics: Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Fluorescence; Humans; Liver Neoplasms; Nicotiana; Photons; Quantum Dots; Sulfhydryl Compounds; Tellurium

Cadmium telluride (CdTe) nanoparticles exhibit strong and stable fluorescence that is attractive for many applications such as biological probing and solid state lighting. The evaluation of nanoparticle toxicity is important for realizing these practical applications. However, no systematic studies of CdTe nanoparticle toxicity have been reported. We investigated and compared the size- and concentration-dependent cytotoxicity of CdTe nanoparticles in human hepatoma HepG2 cells using the MTT assay. CdTe nanoparticles elicited cytotoxicity in a concentration- and size-dependent manner, with smaller-sized particles exhibiting somewhat higher potency. Lesser cytotoxicity of partially purified CdTe-Red particles (following methanol precipitation and resuspension) suggested that free cadmium ions may contribute to cytotoxicity. We also evaluated the acute toxicity of CdTe-Red particles following intravenous exposure in male rats (2 micromol/kg). Few signs of functional toxicity or clinical (urinary or blood) changes were noted. Interestingly, motor activity was transiently reduced (2 hours after treatment) and then significantly increased at a later timepoint (24 hours after dosing). These studies provide a framework for further characterizing the in vitro and in vivo toxic potential of different types of CdTe nanoparticles and suggest that the nervous system may be targeted by these nanoparticles under some conditions.

Topics: Animals; Antineoplastic Agents; Body Weight; Cadmium Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Drug; Hepatocytes; Humans; In Vitro Techniques; Injections, Intravenous; Liver Neoplasms; Male; Motor Activity; Nanoparticles; Nervous System; Particle Size; Rats; Rats, Sprague-Dawley; Tellurium