tellurium and arginyl-glycyl-aspartic-acid

As the early detection and total destruction of gliomas are essential for longer survival, we attempted to synthesize a quantum dot (QD) that is capable of recognizing glioma cells for imaging and photodynamic therapy.. Using a one-pot aqueous approach, near infrared-emitting CdTe was produced. After detection of its physicochemical characteriistics, it was conjugated with RGD. The emission images were observed with confocal microscopy. To test its toxicity, CdTe-RGD at various concentrations was separately added to a human glioma cell line (U251) and a mouse embryo fibroblast cell line (3T3) (control) for incubation in dark conditions. To test its photodynamic effect, the U251 and 3T3 cells were then irradiated for 5-60 min, using a 632.8-nm laser.. This QD (Φ = 3.75 nm, photoluminescence (PL) peak wavelength = 700 nm, photoluminescence quantum yield (PLQY) = 20 %), was a spherical crystal with excellent monodispersity. Under a confocal microscope, U251 cells were visualized, but not the 3T3 cells. In dark conditions, the survival rates of both U251 and 3T3 cells were above 85 %. After laser irradiation, the survival rate of U251 cells decreased to 37 ± 1.6 % as the irradiation time and the CdTe-RGD concentration were increased.. With good physicochemical characteriistics and low toxicity, this QD-RGD has broad prospects for use in the biomedical imaging and photodynamic therapy of gliomas.

Topics: 3T3 Cells; Animals; Antineoplastic Agents; Brain Neoplasms; Cadmium Compounds; Cell Line, Tumor; Cell Survival; Glioblastoma; Glioma; Humans; In Vitro Techniques; Low-Level Light Therapy; Mice; Microscopy, Confocal; Oligopeptides; Photochemotherapy; Quantum Dots; 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

Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvβ3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine-glycine-aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvβ3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.. A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). Phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically.. After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination.. Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD.

Topics: Animals; Cadmium Compounds; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Oligopeptides; Oxidative Stress; Quantum Dots; Selenium Compounds; Sulfides; Tellurium; Tissue Distribution; Toxicity Tests; Zinc Compounds

The purpose of this study was to test the efficacy of cyclic Arg-Gly-Asp (RGD) peptide conjugated with polyionic complex nanomicelles as targeted therapy for glioma.. A stable cyclic RGD polyionic complex nanostructure, ie, a c(RGDfC) polyionic complex micelle, was synthesized and its biocompatibility with cultured neurons was assessed using a cell viability assay. Targeted binding to cultured glioma cells was evaluated by the CdTe quantum dot marking technique and a cell viability assay. The inhibitory effect of the nanomicelles against glioma cells was also evaluated, and their targeted migration into rat brain glioma cells and apoptotic effects were traced by the CdTe quantum dot marking and immunohistochemical staining.. c(RGDfC) polyionic complex micelles did not affect the growth of neurons but bonded selectively to and inhibited proliferation of glioma cells in vitro. When tested in vivo, the micelles migrated into glioma cells, inducing apoptosis in the rat brain.. The c(RGDfC) polyionic complex micelle is an effective targeted therapy against glioma.

Topics: Analysis of Variance; Animals; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Cadmium Compounds; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Drug Delivery Systems; Glioma; Hydrogen-Ion Concentration; Immunohistochemistry; Materials Testing; Micelles; Neurons; Oligopeptides; Quantum Dots; Rats; Rats, Wistar; Tellurium; Xenograft Model Antitumor Assays

We have designed a series of short RGD peptide ligands and developed one-pot aqueous synthesis of integrin-binding CdTe and CdZnTe quantum dots (QDs). We first examined the effects of different RGD peptides, including RGDS, CRGDS, Ac-CRGDS, CRGDS-CONH₂, Ac-CRGDS-CONH₂, RGDSC, CCRGDS, and CCCRGDS, on the synthesis of CdTe QDs. CRGDS were found to be the optimal ligand, providing the CdTe QDs with well-defined wavelength ranges (500-650 nm) and relatively high photoluminescence quantum yields (up to 15%). The key synthesis parameters (the pH value of the Cd²⁺-RGD precursors and the molar ratio of RGD/Cd²⁺) were assessed. In order to further improve the optical properties of the RGD-capped QDs, zinc was then incorporated by the simultaneous reaction of Cd²⁺ and Zn²⁺ with NaHTe. By using a mixture of CRGDS and cysteine as the stabilizer, the quantum yields of CdZnTe alloy QDs reached as high as 60% without any post-treatment, and they also showed excellent stability against time, pH, and salinity. Note that these properties could not be obtained with CRGDS or cysteine alone as the stabilizer. Finally, we demonstrated that the RGD-capped QDs preferentially bind to cell surfaces because of the specific recognition of the RGD sequence to cell surface integrin receptors. Our synthesis strategy based on RGD peptides thus represents a convenient route for opening up QD technologies for cell-specific tagging and labeling applicable to a wide range of diagnostics and therapy.

Topics: Cadmium Compounds; Crystallization; HeLa Cells; HL-60 Cells; Humans; Integrins; Materials Testing; Microscopy, Fluorescence; Oligopeptides; Quantum Dots; Subcellular Fractions; Tellurium; Zinc

A novel dualmodality probe was prepared by linking (188)Re-HGRGD (D) F with CdTe QDs, which was monitored using radio-thin layer chromatography (TLC) and -high performance liquid chromatography (HPLC). The (188)Re-HGRGD (D) F-CdTe QDs probe possesses a radiochemistry yield of 92.1% and strong photoluminescence (PL) stability. However, the radiochemical purity of (188)Re-HGRGD (D) F-QDs would reduce to 74.8%, which should be further improved, after incubation with newborn calf serum (NCF) for 24h. Human glioblastoma U87MG cells, known to express a high-affinity to RGD, were used to assess the in vitro cell binding of probe. The results showed that the radio-signal was in accord with the change of PL intensity, which meant the successful integration of (188)Re and QDs.

Topics: Biological Transport; Cadmium Compounds; Cell Line, Tumor; Humans; Oligopeptides; Quantum Dots; Radiochemistry; Radioisotopes; Rhenium; Tellurium