tellurium and Liver-Neoplasms

The rapid developments in nanotechnology have brought increased attention to the safety of Quantum Dots (QDs). Exploring their mechanisms of toxicity and characterizing their toxic effects in different cell lines will help us better understand and apply QDs appropriately. This study aims to elucidate the importance of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-induced autophagy for CdTe QDs toxicity, that is, the importance of the nanoparticles in mediating cellular uptake and consequent intracellular stress effects inside the cell. The results of the study showed that cancer cells and normal cells have different cell outcomes as a result of intracellular stress effects. In normal human liver cells (L02), CdTe QDs leads to ROS generation and prolong ER stress. The subsequent autophagosome accumulation eventually triggers apoptosis by activating proapoptotic signaling pathways and the expression of proapoptotic Bax. In contrast, in human liver cancer cells (HepG2 cells), expression of UPR restrains proapoptotic signaling and downregulates Bax, and activated protective cellular autophagy, as a result of protecting these liver cancer cells from CdTe QDs-induced apoptosis. In summary, we assess the safety of CdTe QDs and recounted the molecular mechanism underlying its nanotoxicity in normal and cancerous cells. Notwithstanding, additional detailed studies on the deleterious effects of these nanoparticles in the organisms of interest are required to ensure low-risk application.

Topics: Apoptosis; Autophagy; bcl-2-Associated X Protein; Cadmium Compounds; Cell Line; Endoplasmic Reticulum Stress; Humans; Liver Neoplasms; Quantum Dots; Reactive Oxygen Species; Tellurium

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

Topics: Cadmium Compounds; Cell Line; Humans; Liver Neoplasms; Mitochondrial Dynamics; Mitophagy; Quantum Dots; Tellurium

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

To determine the influence of weight, height, gender, age, heart rate, and blood pressure on count rate in cadmium-zinc-telluride single-photon emission computed tomography (CZT SPECT) gated radionuclide angiography.. A total of 1,065 eligible patients referred for routine assessment of left ventricular ejection fraction were registered from August 2015 to November 2016. Data were recorded on heart rate, systolic and diastolic blood pressure, age, gender, height, weight, and count rate. All radionuclide angiographies were performed on a dedicated cardiac CZT SPECT camera, GE Discovery 530c. A dose of 550 MBq. Count rate varied from 1.2 to 8.9 counts per second. All test variables were significantly associated with count rate. From the preliminary analysis, weight appeared as the main contributing factor for explaining the variations in count rate with and R. Patient height, weight, gender, and age have significant impact on count rate when performing CZT radionuclide angiography and may subsequently be used for individualized planning of tracer dosage.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiography; Anthropometry; Blood Pressure; Breast Neoplasms; Cadmium; Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; Cardiomyopathies; Female; Heart Rate; Humans; Kidney Neoplasms; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Middle Aged; Ovarian Neoplasms; Quality Control; Regression Analysis; Retrospective Studies; Tellurium; Young Adult; Zinc

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

To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells.

Topics: Animals; Apoptosis; Breast Neoplasms; Cadmium Compounds; Cattle; Cell Survival; Cells, Cultured; Female; Fluorescence; Fluorescent Dyes; Glycyrrhetinic Acid; Humans; Liver Neoplasms; Oligopeptides; Quantum Dots; Serum Albumin, Bovine; Tellurium

Organic Te(IV) compounds (organotelluranes) differing in their labile ligands exhibited anti-integrin activities in vitro and anti-metastatic properties in vivo. They underwent ligand substitution with l-cysteine, as a thiol model compound. Unlike inorganic Te(IV) compounds, the organotelluranes did not form a stable complex with cysteine, but rather immediately oxidized it. The organotelluranes inhibited integrin functions, such as adhesion, migration, and metalloproteinase secretion mediation in B16F10 murine melanoma cells. In comparison, a reduced derivative with no labile ligand inhibited adhesion of B16F10 cells to a significantly lower extent, thus pointing to the importance of the labile ligands of the Te(IV) atom. One of the organotelluranes inhibited circulating cancer cells in vivo, possibly by integrin inhibition. Our results extend the current knowledge on the reactivity and mechanism of organotelluranes with different labile ligands and highlight their clinical potential.

Topics: Animals; Antineoplastic Agents; Cell Adhesion; Cell Line, Tumor; Cell Movement; Disease Models, Animal; Integrin alpha4beta1; Integrins; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Organometallic Compounds; Protein Binding; Tellurium; Transplantation, Homologous

Hypoxia is a characteristic of cancer and plays a key role in tumorigenesis, angiogenesis and resistance to cancer therapies. SiRNA treatment is effective against hypoxic tumors by gene silencing. However, siRNA delivery to the hypoxic regions of solid tumors still presents a challenge due to the distance from blood vessels and the increased presence of efflux transporters. Therefore, tumor therapies would be improved through the immediate development of an effective siRNA delivery system to hypoxic regions. To this end, we synthesized a system to deliver HIF-1α siRNA into hypoxic tumor cells. The system consists of a functional shell composed of 2-deoxyglucose (DG)-polyethylene glycol (PEG) connected with the compound of lipoic acid, lysine and 9-poly-d-arginine (LA-Lys-9R) by a hydrazone bond and a core of CdTe quantum dots (QDs). The molecular structure of DG-PEG-LA-Lys-9R was confirmed by liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The multifunctional CdTe QDs measured approximately 200 nm and showed excellent biocompatibility, perfect siRNA binding capability and enhanced hypoxic tumor targeting. Importantly, the system described here is pH-responsive with a hydrazone bond; therefore, it avoids GLUT1 receptor-mediated endocytic recycling, resulting in irreversible delivery of the siRNA. We used Western blots to confirm the superior gene silencing efficiency induced by the DG-PEG-LA-Lys-9R with hydrazone modified CdTe QDs. Here, we demonstrate high efficacy of the siRNA tumor delivery system using in vitro and in vivo experiments. In addition, these studies demonstrate that pH-responsive hybrid quantum dots show improved antitumor efficacy with decreased organ toxicity, indicating a promising siRNA delivery system for hypoxic cancer therapy.

Topics: Animals; Cadmium Compounds; Cell Hypoxia; Cell Survival; Deoxyglucose; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Glucose Transporter Type 1; Hep G2 Cells; Humans; Hydrazones; Hydrogen-Ion Concentration; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Lysine; MCF-7 Cells; Mice, Inbred BALB C; Mice, Nude; Oxygen; Peptides; Polyethylene Glycols; Quantum Dots; RNA, Small Interfering; RNAi Therapeutics; Tellurium; Thioctic Acid; Time Factors; Tumor Burden; Tumor Microenvironment; Xenograft Model Antitumor Assays

Using the intrinsic toxicity of nanomaterials for anticancer therapy is an emerging concept. In this work, we discovered that CdTe/CdS quantum dots, when coated with lipids (QD-LC) instead of popular liposomes, polymers, or dendrimers, demonstrated extraordinarily high specificity for cancer cells, which was due to the difference in the macropinocytosis uptake pathways of QD-LC between the cancer cells and the normal cells. QD-LC-induced HepG2 cell apoptosis was concomitant with the activation of the JNK/caspase-3 signaling pathway. Moreover, QD-LC treatment resulted in a delay in the latent period for microtumor formation of mouse hepatocarcinoma H22 cells and inhibited tumor growth, with a reduction of 53.2% in tumor volume without toxicity in major organs after intratumoral administrations to tumor-bearing mice. Our results demonstrate that QD-LC could be a very promising theranostic agent against liver cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cadmium Compounds; Cell Survival; Endocytosis; Hep G2 Cells; Humans; Lipids; Liver Neoplasms; Male; Mice; Mice, Inbred ICR; Quantum Dots; Selenium Compounds; 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

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

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

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