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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of carbon nanotubes (CNTs) on living systems such as cells are crucial for the safe development of biosensors, drug carriers, or tumor imaging agents. We report here that SWCNT-COOH inhibited cell proliferation via a nonapoptotic mechanism, which is different from effects caused by pristine CNTs. On the basis of SWCNT-COOH's perturbations on cells, expression of genes and protein, and protein phosphorylations, we conclude that SWCNT-COOH suppresses Smad-dependent bone morphogenetic protein (BMP) signaling pathway and down-regulates Id proteins. These molecular events cause cell cycle arrest at G(1)/S transition and inhibit cell proliferation. The specific suppression of BMP signaling and Id proteins by SWCNT-COOH demonstrates nonapoptotic effects of functionalized CNTs on human cells. This finding may have potential therapeutic applications to treat human diseases related to Id proteins or BMP signaling such as breast cancer and bone diseases.
ACS Nano 2009 May 26
PMID:Suppression of human bone morphogenetic protein signaling by carboxylated single-walled carbon nanotubes. 1940 38

Tumor-specific gene delivery constitutes a primary challenge in nonviral mediated gene therapy. In this investigation, branched polyethylenimine (bPEI, 25 kDa) was modified by forming nanoconstructs with a natural polysaccharide, chondroitin sulfate (CS), to impart site-specific property. A library of CS-PEI (CP) nanoconstructs was fabricated by altering the content of CS and evaluated in terms of size, surface charge, morphology, pDNA loading efficiency, pDNA release assay, pDNA protection study, cytotoxicity, and transfection efficiency. In vitro transfection efficiency of CP nanoconstructs was examined in HEK293, HEK293T, HepG2, and HeLa cell lines, while their cytotoxicity was investigated in HepG2 and HeLa cells. DNase I protection assay showed that the plasmid was protected from degradation over a period of time. The CP nanoconstructs possess significantly lower toxicity and enhanced transfection efficiency compared to PEI (25 kDa) and commercial transfection reagents (i.e., superfect, fugene, and GenePORTER 2). Further, the CP nanoconstructs were also found to transfect cells in serum-containing medium. In vivo studies were carried out with pDNA loaded CP-3 nanoconstruct after intravenous (iv) injection in Ehrlich ascites tumor (EAT)-bearing mice. The outcome revealed higher concentration of CP-3 nanoconstruct in tumor mass. These findings demonstrate that CP nanoconstructs could be exploited as carriers for nanomedicine for efficient management of solid tumor.
ACS Nano 2009 Jun 23
PMID:Gene expression, biodistribution, and pharmacoscintigraphic evaluation of chondroitin sulfate-PEI nanoconstructs mediated tumor gene therapy. 1944 35

Upconversion fluorescent nanoparticles can convert a longer wavelength radiation (e.g., near-infrared light) into a shorter wavelength fluorescence (e.g., visible light) and thus have emerged as a new class of fluorescent probes for biomedical imaging. Rare-earth doped beta-NaYF(4):Yb,Er upconversion nanoparticles (UCNPs) with strong UC fluorescence were synthesized in this work by using a solvothermal approach. The UCNPs were coated with a thin layer of SiO(2) to form core-shell nanoparticles via a typical Stober method, which were further modified with amino groups. After surface functionalization, the rabbit anti-CEA8 antibodies were covalently linked to the UCNPs to form the antibody-UCNP conjugates. The antibody-UCNP conjugates were used as fluorescent biolabels for the detection of carcinoembryonic antigen (CEA), a cancer biomarker expressed on the surface of HeLa cells. The successful conjugation of antibody to the UCNPs was found to lead to the specific attachment of the UCNPs onto the surface of the HeLa cells, which further resulted in the bright green UC fluorescence from the UCNP-labeled cells under 980 nm near-infrared (NIR) excitation and enabled the fluorescent imaging and detection of the HeLa cells. These results indicate that the amino-functionalized UCNPs can be used as fluorescent probes in cell immunolabeling and imaging. Because the UCNPs can be excited with a NIR light to exhibit strong visible fluorescence and the NIR light is safe to the body and can penetrate tissue as deep as several inches, our work suggests that, with proper cell-targeting or tumor-homing peptides or proteins conjugated, the NaYF(4):Yb,Er UCNPs can find potential applications in the in vivo imaging, detection, and diagnosis of cancers.
ACS Nano 2009 Jun 23
PMID:Immunolabeling and NIR-excited fluorescent imaging of HeLa cells by using NaYF(4):Yb,Er upconversion nanoparticles. 1947 17

The inhibitor of apoptosis (IAP) proteins are critical regulators of cancer cell survival, which makes them attractive targets for therapeutic intervention in cancers. Herein, we describe the structure-based design of IAP antagonists with high affinities and selectivity (>2000-fold) for c-IAP1 over XIAP and their functional characterization as activators of apoptosis in tumor cells. Although capable of inducing cell death and preventing clonogenic survival, c-IAP-selective antagonists are significantly less potent in promoting apoptosis when compared to pan-selective compounds. However, both pan-IAP- and c-IAP-selective antagonists stimulate c-IAP1 and c-IAP2 degradation and activation of NF-kappaB pathways with comparable potencies. Therefore, although compounds that specifically target c-IAP1 and c-IAP2 are capable of inducing apoptosis, antagonism of the c-IAP proteins and XIAP is required for efficient induction of cancer cell death by IAP antagonists.
ACS Chem Biol 2009 Jul 17
PMID:Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists. 1958 16

Rare-earth up-converting nanophosphors (UCNPs) have great potential to become a new generation of biological luminescent labels, but their use has been limited by difficulties in obtaining water-soluble UCNPs bearing appropriate functional groups. To address this problem, we report herein a simple and efficient procedure for the preparation of amine-functionalized UCNPs by a modified hydrothermal microemulsion route assisted with 6-aminohexanoic acid. The amine content of the resultant UCNPs has been determined to be (9.5+/-0.8) x 10(-5) mol/g, which not only confers excellent dispersibility in aqueous solution, but also allows further conjugation with targeted molecules such as folic acid (FA) as a ligand. By means of the laser scanning up-conversion luminescence microscopy (LSUCLM) and the in vivo up-conversion luminescence (UCL) imaging under excitation at the CW infrared laser at 980 nm, FA-coupled UCNPs have been demonstrated to be effective in targeting folate-receptor overexpressing HeLa cells in vitro and HeLa tumor in vivo and ex vivo. These results indicated that our UCNPs could be used as whole-body targeted UCL imaging agents.
 ...
PMID:Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors. 1956 39

Magnetic nanoparticles (MNP) can be used as contrast-enhancing agents to visualize tumors by magnetic resonance imaging (MRI). Here we describe an easy synthesis method of magnetic nanoparticles coated with polyethylene glycol (PEG) and demonstrate size-dependent accumulation in murine tumors following intravenous injection. Biocompatible iron oxide MNPs coated with PEG were prepared by replacing oleic acid with a biocompatible and commercially available silane-PEG to provide an easy and effective method for chemical coating. The colloidal stable PEGylated MNPs were magnetically separated into two distinct size subpopulations of 20 and 40 nm mean diameters with increased phagocytic uptake observed for the 40 nm size range in vitro. MRI detection revealed greater iron accumulation in murine tumors for 40 nm nanoparticles after intravenous injection. The enhanced MRI contrast of the larger MNPs in the tumor may be a combined result of the size-dependent extravasation and capture by macrophages in the tumor, providing important considerations for improved bioimaging approaches.
ACS Nano 2009 Jul 28
PMID:Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors. 1957 20

At present, nanofilaments are not exclusively based on carbon atoms but can be produced from many inorganic materials in the form of nanotubes and nanowires. It is essential to systematically assess the acute toxicity of these newly synthesized materials since it cannot be predicted from the known toxicity of the same material in another form. Here, the cellular toxicity of TiO2-based nanofilaments was studied in relation to their morphology and surface chemistry. These structures produced by hydrothermal treatment were titanate nanotubes and nanowires with a Na(x)TiO(2+delta) composition. The cytotoxic effect was mainly evaluated by MTT assays combined with direct cell counting and cytopathological analyses of the lung tumor cells. Our work clearly demonstrated that the presence of Na(x)TiO(2+delta) nanofilaments had a strong dose-dependent effect on cell proliferation and cell death. Nanofilament internalization and alterations in cell morphology were observed. Acid treatment performed to substitute Na(+) with H(+) in the Na(x)TiO(2+delta) nanofilaments strongly enhanced the cytotoxic action. This effect was attributed to structural imperfections, which are left by the atom diffusion during the substitution. On the basis of our findings, we conclude that TiO2-based nanofilaments are cytotoxic and thus precautions should be taken during their manipulation.
ACS Nano 2009 Aug 25
PMID:Cellular toxicity of TiO2-based nanofilaments. 1961 Jun 3

Oxidation of cysteine to sulfenic acid has emerged as a biologically relevant post-translational modification with particular importance in redox-mediated signal transduction; however, the identity of modified proteins remains largely unknown. We recently reported DAz-1, a cell-permeable chemical probe capable of detecting sulfenic acid modified proteins directly in living cells. Here we describe DAz-2, an analogue of DAz-1 that exhibits significantly improved potency in vitro and in cells. Application of this new probe for global analysis of the sulfenome in a tumor cell line identifies most known sulfenic acid modified proteins: 14 in total, plus more than 175 new candidates, with further testing confirming oxidation in several candidates. The newly identified proteins have roles in signal transduction, DNA repair, metabolism, protein synthesis, redox homeostasis, nuclear transport, vesicle trafficking, and ER quality control. Cross-comparison of these results with those from disulfide, S-glutathionylation, and S-nitrosylation proteomes reveals moderate overlap, suggesting fundamental differences in the chemical and biological basis for target specificity. The combination of selective chemical enrichment and live-cell compatibility makes DAz-2 a powerful new tool with the potential to reveal new regulatory mechanisms in signaling pathways and identify new therapeutic targets.
ACS Chem Biol 2009 Sep 18
PMID:Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. 1964 9

Nanoparticles, including multiwalled carbon nanotubes (MWNTs), strongly absorb near-infrared (nIR) radiation and efficiently convert absorbed energy to released heat which can be used for localized hyperthermia applications. We demonstrate for the first time that DNA-encasement increases heat emission following nIR irradiation of MWNTs, and DNA-encased MWNTs can be used to safely eradicate a tumor mass in vivo. Upon irradiation of DNA-encased MWNTs, heat is generated with a linear dependence on irradiation time and laser power. DNA-encasement resulted in a 3-fold reduction in the concentration of MWNTs required to impart a 10 degrees C temperature increase in bulk solution temperature. A single treatment consisting of intratumoral injection of MWNTs (100 microL of a 500 microg/mL solution) followed by laser irradiation at 1064 nm, 2.5 W/cm(2) completely eradicated PC3 xenograft tumors in 8/8 (100%) of nude mice. Tumors that received only MWNT injection or laser irradiation showed growth rates indistinguishable from nontreated control tumors. Nonmalignant tissues displayed no long-term damage from treatment. The results demonstrate that DNA-encased MWNTs are more efficient at converting nIR irradiation into heat compared to nonencased MWNTs and that DNA-encased MWNTs can be used safely and effectively for the selective thermal ablation of malignant tissue in vivo.
ACS Nano 2009 Sep 22
PMID:Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes. 1965 28

In the present study, we report the novel application of polyhydroxylated fullerenes (fullerenols) in cancer drug delivery. The facile synthetic procedure for generating multiple hydroxyl groups on the fullerene cage offers scope for high drug loading in addition to conferring hydrophilicity. Doxorubicin, a first line cancer chemotherapeutic, was conjugated to fullerenols through a carbamate linker, achieving ultrahigh loading efficiency. The drug-fullerenol conjugate was found to be relatively stable in phosphate buffer saline but temporally released the active drug when incubated with tumor cell lysate. The fullerenol-doxorubicin conjugate suppressed the proliferation of cancer cell-lines in vitro through a G2-M cell cycle block, resulting in apoptosis. Furthermore, in an in vivo murine tumor model, fullerenol-doxorubicin exhibited comparable antitumor efficacy as free drug without the systemic toxicity of free doxorubicin. Additionally, we demonstrate that the fullerenol platform can be extended to other chemotherapeutic agents, such as the slightly water-soluble cisplatin, and can emerge as a new paradigm in the management of cancer.
ACS Nano 2009 Sep 22
PMID:Fullerenol-cytotoxic conjugates for cancer chemotherapy. 1968 36


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