ABSTRACT
Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment.
Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Selenium/therapeutic use , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Apoptosis/drug effects , Camptothecin/administration & dosage , Camptothecin/therapeutic use , Cell Line, Tumor , Female , Humans , Irinotecan , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/administration & dosage , Neoplasms/metabolism , Neoplasms/pathology , Rats , Selenium/administration & dosageABSTRACT
Myocardial ischemia is featured by a significant increase in the cytoplasm proton concentration, and such a proton change may be applied as an index for earlier ischemic heart disease diagnostics. But such a pH change in a live heart cell is difficult to monitor as a normal fluorescent probe cannot specifically transport into the cytoplasm of an ischemic cell. This is because the heart cell contains condensed myofibrils which are tight barriers for a normal probe to penetrate. We design fluorescent probes, single-strand DNA wrapped single-wall carbon nanotubes (ssDNA-SWCNTs), where the ssDNA is labeled by the dye molecule hexachloro-6-carboxyfluorescein (HEX). This nanoprobe could transport well into a live heart cell and locate in the cytoplasm to sensitively detect the intracellular pH change of myocardial ischemia. Briefly, protons neutralize the negative charges of nanoprobes in the cytoplasm. This will weaken the stability of nanoprobes and further tune their aggregation. Such aggregations induce the HEX of some nanoprobes condensed together and further result in their fluorescence quenching. The nanoprobes are advantaged in penetrating condensed myofibrils of the heart cell, and their fluorescence intensity is sensitive to the proton concentration change in the live cell cytoplasm. This new method may provide great assistance in earlier cardiopathy diagnosis in the future.
Subject(s)
Carbon/chemistry , Cytoplasm/metabolism , DNA, Single-Stranded/chemistry , Myocardial Ischemia/metabolism , Nanotubes , Hydrogen-Ion ConcentrationABSTRACT
A probe composed of an aptamer and a silver cluster, where the aptamer targets mIgM of live cells and the silver cluster provides fluorescent imaging and mass quantification of mIgM of live cells, is presented. This new probe simultaneously provides accurate spatial and mass information of mIgM in live cells.
Subject(s)
Aptamers, Nucleotide/chemistry , Immunoglobulin M/analysis , Silver/chemistry , Biosensing Techniques , Cell Line, Tumor , Cell Membrane , Fluorescence , HumansABSTRACT
Polyethylene glycol modified graphene oxide (GO-PEG) nanoparticles were prepared, which were positively charged and fairly stable in buffer solution. The GO-PEG nanoparticles possess a special affinity to the plasma membrane of live cells, and their yellowish-green fluorescence is sensitively responsive to the extracellular physiological solution in situ.
Subject(s)
Cell Membrane/metabolism , Extracellular Space/chemistry , Graphite/pharmacology , Oxides/pharmacology , Polyethylene Glycols/pharmacology , Tumor Microenvironment , Cell Survival/drug effects , Graphite/chemistry , HeLa Cells , Humans , Hydrogen-Ion Concentration , Nanoparticles/chemistry , Oxides/chemistry , Polyethylene Glycols/chemistryABSTRACT
A bifunctional peptide was designed to in situ reduce Cu ions and anchor a Cu cluster. The peptide-Cu cluster probe, mainly composed of Cu14, emitted blue two-photon fluorescence under femtosecond laser excitation. Most important, the probe can specifically mark the nuclei of HeLa and A549 cells, respectively.
Subject(s)
Cell Nucleus/physiology , Copper/chemistry , Oligopeptides , Cell Line , Fluorescence , HeLa Cells , Humans , Oligopeptides/chemical synthesis , Photons , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrophotometry, UltravioletABSTRACT
A terbium based fluorescent probe was synthesized by coordinating terbium ions with a designed oligonucleotides (5'-ATATGGGGGATAT-3', termed GH5). GH5 improved the fluorescence of terbium ions by four orders of magnitude. The fluorescence enhancement of terbium ions by different oligonucleotides sequences indicated that the polyguanine loop of the hairpin GH5 is key to enhance terbium ion emission. The quantum yield of Tb-GH5 probe was 10.5% and the probe was photo-stable. The result of conductivity titration indicated that the stoichiometry of the probe is 3.5 Tb: 1 GH5, which is confirmed by fluorescence titration. This probe had high sensitivity and specificity for the detection of lead ions. The fluorescence intensity of this probe was linear with respect to lead concentration over a range 0.3-2.1 nM (R(2) = 0.99). The limit of detection for lead ions was 0.1 nM at a signal-to-noise ratio of 3.
Subject(s)
Fluorescent Dyes/chemistry , Lead/analysis , Oligonucleotides/chemistry , Terbium/chemistry , Inverted Repeat Sequences , Lead/chemistry , Limit of Detection , Poly G/chemistry , Spectrometry, FluorescenceABSTRACT
Luminescent silver nanoclusters were anchored by designed oligonucleotides. After hybridizing with human telomerase RNA template, the luminescence of the cluster decreased linearly with respect to the concentration of the complementary strand (25-250 nM). The cluster is therefore a potential candidate for human telomerase detection.
Subject(s)
Luminescent Agents/chemistry , Nanostructures/chemistry , Oligonucleotides/chemistry , RNA/analysis , Silver/chemistry , Telomerase/analysis , Base Sequence , Humans , Luminescent Measurements/methods , Sensitivity and Specificity , Templates, GeneticABSTRACT
Silver cluster-aptamer hybrids were mineralized via an artificially designed aptamer. The hybrids gave red emission when excited by light, and they successfully targeted the nucleus of live cells. This method is an effective approach to make cell target probes.
Subject(s)
Aptamers, Nucleotide/chemistry , Cell Nucleus/pathology , Silver/chemistry , Benzimidazoles/chemistry , Cell Line , Cell Nucleus/chemistry , Humans , Microscopy, Confocal , SELEX Aptamer TechniqueABSTRACT
The artificial peptide with amino acid sequence CCYRGRKKRRQRRR was used to biomineralize serial Ag clusters. Under different alkaline conditions, clusters with red and blue emission were biomineralized by the peptide, respectively. The matrix-assisted laser desorption/ionization time-of-flight mass spectra implied that the red-emitting cluster sample was composed of Ag(28), while the blue-emitting cluster sample was composed of Ag(5), Ag(6), and Ag(7). The UV-visible absorption and infrared spectra revealed that the peptide phenol moiety reduced Ag(+) ions and that formed Ag clusters were captured by peptide thiol moieties. The phenol reduction potential was controlled by the alkalinity and played an important role in determining the Ag cluster size. Circular dichroism observations suggested that the alkalinity tuned the peptide secondary structure, which may also affect the Ag cluster size.
Subject(s)
Minerals/metabolism , Peptides/metabolism , Silver/chemistry , Silver/metabolism , Absorption , Active Transport, Cell Nucleus , Amino Acid Sequence , Cell Nucleus/metabolism , Hydrogen-Ion Concentration , Molecular Imaging , Molecular Sequence Data , Peptides/chemistry , Protein Sorting Signals , tat Gene Products, Human Immunodeficiency Virus/chemistryABSTRACT
The biomaterials used for central nervous system injury require not only interacting with specific cell adhesion but also specific growth factor receptors to promote nerve regeneration. In this study, hyaluronic acid (HA)-based hydrogels modified with poly-L-lysine (PLL) and nogo-66 receptor antibody (antiNgR) (HA-PLL/antiNgR) were administered to rats after lateral hemisection of the spinal cord. Anti-neurofilament positive axons were found to extend into the HA-PLL/antiNgR hydrogel at 8 weeks after implantation, which shows significant difference compared with HA-PLL or blank control group. Electron micrographs of implanted hydrogels showed that there were more cells and normal axons with myelin in the HA-PLL/antiNgR implant than that of HA-PLL hydrogel. The antiNgR grafted on HA hydrogels could be detected for 8 weeks after transplantation in vivo. All of these properties may facilitate HA-PLL/antiNgR hydrogels to become a promising scaffold for repairing spinal cord injury. Nevertheless, both two kinds of modified hydrogels (HA-PLL/antiNgR and HA-PLL) showed remarkable advantages in supporting angiogenesis, and simultaneously inhibiting the formation of glial scar.