12,161 research outputs found

    Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications.

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    Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed

    Anti-angiogenesis therapy based on the bone marrow-derived stromal cells genetically engineered to express sFlt-1 in mouse tumor model

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    <p>Abstract</p> <p>Background</p> <p>Bone marrow-derived stromal cells (BMSCs) are important for development, tissue cell replenishment, and wound healing in physiological and pathological conditions. BMSCs were found to preferably reach sites undergoing the process of cell proliferation, such as wound and tumor, suggesting that BMSCs may be used as a vehicle for gene therapy of tumor.</p> <p>Methods</p> <p>Mouse BMSCs were loaded with recombinant adenoviruses which express soluble Vascular Endothelial Growth Factor Receptor-1 (sFlt-1). The anti-angiogenesis of sFlt-1 in BMSCs was determined using endothelial cells proliferation inhibition assay and alginate encapsulation assay. The anti-tumor effects of BMSCs expressing sFlt-1 through tail-vein infusion were evaluated in two mouse tumor metastases models.</p> <p>Results</p> <p>BMSCs genetically modified with Adv-GFP-sFlt-1 could effectively express and secret sFlt-1. BMSCs loaded with sFlt-1 gene could preferentially home to tumor loci and decrease lung metastases and prolong lifespan in mouse tumor model through inducing anti-angiogenesis and apoptosis in tumors.</p> <p>Conclusion</p> <p>We demonstrated that BMSCs might be employed as a promising vehicle for tumor gene therapy which can effectively not only improve the concentration of anticancer therapeutics in tumors, but also modify the tumor microenvironment.</p

    Blue laser directed energy deposition of aluminum with synchronously enhanced efficiency and quality

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    Directed energy deposition (DED) of aluminum with infrared lasers faces many processing issues, e.g., poor formability, pore formation, high reflectivity, all lowering the productivity. In this paper, we developed and applied a 2 kW high-power (450 nm) blue laser directed energy deposition (BL-DED) of a nano-TiB2 decorated AlSi10Mg composite. The single-track experiment reveals that the required power density of blue laser to form fully melted track is lower than that of an infrared laser (1060 nm). Under the laser power of 900 W with a scanning speed of 4 mm/s, the width and depth of molten pool is approximately 2500 µm and 350 µm respectively with blue laser, while the powders are not fully melted with infrared laser, owing to aluminum's higher absorption at blue laser wavelengths. The area fraction of equiaxed grains accounts for as high as 63% at 4 mm/s. To the best of our knowledge, this result is the highest area fraction of equiaxed grains in a single-track molten pool of DED process. Such a high fraction is mainly due to the low thermal gradient (8 × 105 K/m) of the flat-top blue laser and the refining effect of nano TiB2 particles. Our work demonstrates that high-power blue laser has enhanced both efficiency and build quality compared to DED of aluminum alloys and composites using an infrared laser, which also promises to help process other high-reflectivity materials like copper alloys

    Superconductivity induced by Ni doping in BaFe2_2As2_2

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    A series of 122 phase BaFe2−x_{2-x}Nix_xAs2_2 (xx = 0, 0.055, 0.096, 0.18, 0.23) single crystals were grown by self flux method and a dome-like Ni doping dependence of superconducting transition temperature is discovered. The transition temperature TconT_c^{on} reaches a maximum of 20.5 K at xx = 0.096, and it drops to below 4 K as xx ≥\geq 0.23. The negative thermopower in the normal state indicates that electron-like charge carrier indeed dominates in this system. This Ni-doped system provides another example of superconductivity induced by electron doping in the 122 phase.Comment: 7 pages, 5 figures, revised version, added EDX result, accepted for special issue of NJ

    Expression, Purification, Characterization and In Vitro Activity of Recombinant Mouse Cu/Zn-Binding Superoxide Dismutase (mSOD1)

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    Purpose: To express, purify and characterize recombinant mouse Cu/Zn-binding superoxide dismutase (mSOD1), and investigate its activity in vitro.Methods: The protein, mSOD1, was expressed after induction with isopropyl-beta-Dthiogalactopyranoside (IPTG). The target protein was purified by Ni-NTA affinity chromatography. The identity of the recombinant protein was confirmed by Western-blot and peptide mass fingerprinting(PMF) analysis. Protein activity in vitro was investigated by SOD activity assay kit and DNA damage protective assay.Results: mSOD1 protein was expressed with a final yield of about 60 mg of pure protein per liter of culture medium. After purification, the target protein was &gt; 95 %. The identity of the recombinant protein was confirmed. SOD activity assay showed that the highest activity of the mSOD1 was 3789.0 ± 80.5 U/mg. The present work showed that mSOD1 was effective in protecting DNA from oxidative damage.Conclusion: High purity recombinant mSOD1 was obtained and  characterized, and had high activity in vitro. The study indicates that the mSOD1 may serve as a potential therapeutic agent for those diseasescaused by oxidative stress.Keywords: Cu/Zn-binding Superoxide dismutase, Expression, Purification, Metal ions, DNA damag
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