20 research outputs found

    Nuclear-Targeting Gold Nanorods for Extremely Low NIR Activated Photothermal Therapy

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    Photorelated nanomedicine is of particular interest as an emerging paradigm toward precise cancer therapy, as demonstrated by recent developments of photothermal therapy (PTT), an emerging technique employing light-converting agents to burn cancerous cells by overdosed optical energy-converted heat. However, most of the laser irradiations needed for effective PTT significantly exceed the maximal permissible power density in human skin, which is likely to damage surrounding normal tissues. Herein, we report a strategy of intranuclear PTT of cancer enabled by nuclear-targeted delivery of gold nanorods of ∼10.5 × 40.5 nm in size via conjugation with nuclear location signal peptides (GNRs-NLS) under an extremely low near-infrared irradiation of 0.2 W/cm<sup>2</sup>, much below the maximal permissible exposure of skin. Interestingly, we found that a mild but nuclear-focused temperature increase generated by GNRs-NLS is sufficient to cause damage to intranuclear DNA and the inhibition of DNA repair process, which, interestingly, led to the cancer cell apoptosis rather than to conventional cell necrosis by thermal ablation during PTT. Correspondingly, tumors treated with GNRs-NLS exhibited gradual but significant regressions rather than traditional harsh burning-up of tumors, in comparison with negligible antitumor effect by GNRs without nuclear targeting under the same ultralow NIR irradiation. This report demonstrates the successful intranuclear efficient photothermal therapy of cancer via cell apoptosis by photoadsorbing agents, e.g., GNRs-NLS in the present case, with largely mitigated side-effect on normal tissues and therefore substantially improved biosafety

    Sorption of U(VI) on MX-80 Bentonite and Granite in Ca-Na-Cl Saline Solutions

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    Uranium has been identified as an element of interest for the safety assessment of a deep geological repository for used nuclear fuel. This paper examines the sorption behavior of U(VI) onto MX-80 bentonite and granite in Ca-Na-Cl solutions of varying ionic strengths [0.05 to 3 mol/kgw (m)] and across a pH range of 4 to 10. U(VI) sorption on MX-80 showed that U(VI) sorption gradually increased with pHm until pHm = 6, where it reached its maximum, and decreased slightly with pHm until pHm = 8, and then became constant. U(VI) sorption on granite increased along with pHm, reached the maximum around pHm = 7 to 8, and then slightly decreased with pHm. Both MX-80 and granite showed essentially no ionic strength dependence for sorption of U(VI). A nonelectrostatic surface complexation model successfully predicted sorption of U(VI) onto MX-80 and granite using the formation of an inner-sphere surface complex. Optimized values of surface complexation reaction constants (log K0) for the formation reactions of these surface species are proposed.</p

    Ultrasensitive Nanosensors Based on Upconversion Nanoparticles for Selective Hypoxia Imaging in Vivo upon Near-Infrared Excitation

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    Hypoxia is a distinct feature of malignant solid tumors, which is a possible causative factor for the serious resistance to chemo- and radiotherapy or the development of invasion and metastasis. The exploration of nanosensors with the capabilities like the accurate diagnosis of hypoxic level will be helpful to estimate the malignant degree of tumor and subsequently implement more effective personalized treatment. Here, we report the design and synthesis of nanosensors that can selectively and reversibly detect the level of hypoxia both in vitro and in vivo. The designed nanosensor is composed of two main moieties: oxygen indicator [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub> for detection of hypoxia and upconversion nanoparticles for offering the excitation light of [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub> by upconversion process under 980 nm exposure. The results show that the nanosensors can reversibly become quenched or luminescent under hyperoxic or hypoxic conditions, respectively. Compared with free [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub>, the designed nanosensors exhibit enhanced sensitivity for the detection of oxygen in hypoxic regions. More attractively, the nanosensors can image hypoxic regions with high penetration depth because the absorption and emission wavelength are within the NIR and far-red region, respectively. Most importantly, nanosensors display a high selectivity for detection of relevant oxygen changes in cells and zebrafish

    Ultrasensitive Nanosensors Based on Upconversion Nanoparticles for Selective Hypoxia Imaging in Vivo upon Near-Infrared Excitation

    No full text
    Hypoxia is a distinct feature of malignant solid tumors, which is a possible causative factor for the serious resistance to chemo- and radiotherapy or the development of invasion and metastasis. The exploration of nanosensors with the capabilities like the accurate diagnosis of hypoxic level will be helpful to estimate the malignant degree of tumor and subsequently implement more effective personalized treatment. Here, we report the design and synthesis of nanosensors that can selectively and reversibly detect the level of hypoxia both in vitro and in vivo. The designed nanosensor is composed of two main moieties: oxygen indicator [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub> for detection of hypoxia and upconversion nanoparticles for offering the excitation light of [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub> by upconversion process under 980 nm exposure. The results show that the nanosensors can reversibly become quenched or luminescent under hyperoxic or hypoxic conditions, respectively. Compared with free [Ru­(dpp)<sub>3</sub>]<sup>2+</sup>Cl<sub>2</sub>, the designed nanosensors exhibit enhanced sensitivity for the detection of oxygen in hypoxic regions. More attractively, the nanosensors can image hypoxic regions with high penetration depth because the absorption and emission wavelength are within the NIR and far-red region, respectively. Most importantly, nanosensors display a high selectivity for detection of relevant oxygen changes in cells and zebrafish

    Additional file 3: of DNA methylation profiles correlated to striped bass sperm fertility

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    Table S2. Differentially methylated regions (DMRs) between high- and sub-fertility striped bass sperm at a strict false discovery rate (FDR) < 0.1 (XLS). (XLS 53 kb

    Additional file 2: of DNA methylation profiles correlated to striped bass sperm fertility

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    Figure S1. Alignment scores (percent of total) of MBD-Seq short reads aligned to the striped bass genome. (PNG 343 kb

    Nuclear-Targeted Drug Delivery of TAT Peptide-Conjugated Monodisperse Mesoporous Silica Nanoparticles

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    Most present nanodrug delivery systems have been developed to target cancer cells but rarely nuclei. However, nuclear-targeted drug delivery is expected to kill cancer cells more directly and efficiently. In this work, TAT peptide has been employed to conjugate onto mesoporous silica nanoparticles (MSNs-TAT) with high payload for nuclear-targeted drug delivery for the first time. Monodispersed MSNs-TAT of varied particle sizes have been synthesized to investigate the effects of particle size and TAT conjugation on the nuclear membrane penetrability of MSNs. MSNs-TAT with a diameter of 50 nm or smaller can efficiently target the nucleus and deliver the active anticancer drug doxorubicin (DOX) into the targeted nucleus, killing these cancer cells with much enhanced efficiencies. This study may provide an effective strategy for the design and development of cell-nuclear-targeted drug delivery

    Additional file 4: of DNA methylation profiles correlated to striped bass sperm fertility

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    Table S3. Annotation of the identified differentially methylated regions (DMRs) in striped bass sperm from high- and sub-fertility groups. Genes present on contigs with DMRs are indicated in the column to the left (DMRs) and are numbered according to the striped bass genome assembly files provided at http://appliedecology.cals.ncsu.edu/striped-bass-genome-project/data-downloads/ . Additional information including start and end of the gene transcripts on each of the contigs, length of the DMR site (Width), methylation levels in fish from the sub-fertile (Conc_Low) and high-fertile (Conc_High) groups, methylation fold-difference between fertility groups (negative value indicates greater in the high fertility group in reference to the low fertility group), p-value, false discovery rate (FDR), gene name (Name), approved gene symbol (Gene), gene position on each of the contigs (Gene Position), and method of annotation (ID) either from the striped bass genome or BLAST of the National Center for Biotechnology Information (XLS). (XLS 91 kb

    Highly Sensitive Diagnosis of Small Hepatocellular Carcinoma Using pH-Responsive Iron Oxide Nanocluster Assemblies

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    Iron oxide nanoparticle (IONP)-based magnetic resonance imaging (MRI) contrast agents have been widely used for the diagnosis of hepatic lesions. However, current IONP-based liver-specific MRI contrast agents rely on single-phase contrast enhancement of the normal liver, which is not sensitive enough to detect early stage small hepatocellular carcinomas (HCCs). We herein report i-motif DNA-assisted pH-responsive iron oxide nanocluster assemblies (termed RIAs), which provide an inverse contrast enhancemt effect to improve the distinction between normal liver and target HCC tissues. The acidic pH of the tumor microenvironment triggers the disassembly of the RIAs, which leads to a drastic decrease in their relaxivity ratio (<i>r</i><sub>2</sub>/<i>r</i><sub>1</sub>), thus converting the RIAs from a T2 to T1 contrast agent. This inverse contrast enhancement of normal liver darkening and HCC brightening under T1 imaging mode was validated on an orthotopic HCC model. Our design provides a novel strategy for the exploitation of the next-generation intelligent MRI contrast agents
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