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Results: 1 to 10 of 63

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Nanotechnology in Neuroscience Reveals Membrane Mobility Matters.
Rosenthal SJ
(2019) ACS Chem Neurosci 10: 30-32
MeSH Terms: Animals, Cell Membrane, Humans, Membrane Transport Proteins, Nanotechnology, Neurosciences, Quantum Dots
Show Abstract · Added March 26, 2019
Quantum dots are nanometer-sized semiconductors that have size-tunable, narrow emission bands, high quantum yields, and are resistant to photobleaching. Ligand-conjugated quantum dots enable the real time visualization of membrane proteins and have revealed that membrane diffusion dynamics are intrinsic to protein regulation, are susceptible to the level of membrane cholesterol, and are altered in genetic variants linked to disease, suggesting a mise en place approach to neuropsychopharmacology.
0 Communities
1 Members
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7 MeSH Terms
Nanotechnology Enabled Modulation of Signaling Pathways Affects Physiologic Responses in Intact Vascular Tissue.
Hocking KM, Evans BC, Komalavilas P, Cheung-Flynn J, Duvall CL, Brophy CM
(2019) Tissue Eng Part A 25: 416-426
MeSH Terms: Actin Cytoskeleton, Actins, Animals, Blood Vessels, Calcium, Gene Silencing, Heat-Shock Proteins, Humans, Micelles, Muscle Contraction, Muscle, Smooth, Nanoparticles, Nanotechnology, Peptides, Polymerization, RNA, Small Interfering, Rats, Signal Transduction, Static Electricity
Show Abstract · Added April 10, 2019
IMPACT STATEMENT - Subarachnoid hemorrhage (SAH) is associated with vasospasm that is refractory to traditional vasodilators, and inhibition of vasospasm after SAH remains a large unmet clinical need. SAH causes changes in the phosphorylation state of the small heat shock proteins (HSPs), HSP20 and HSP27, in the vasospastic vessels. In this study, the levels of HSP27 and HSP20 were manipulated using nanotechnology to mimic the intracellular phenotype of SAH-induced vasospasm, and the effect of this manipulation was tested on vasomotor responses in intact tissues. This work provides insight into potential therapeutic targets for the development of more effective treatments for SAH induced vasospasm.
0 Communities
2 Members
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19 MeSH Terms
Shape-engineered multifunctional porous silicon nanoparticles by direct imprinting.
Mares JW, Fain JS, Beavers KR, Duvall CL, Weiss SM
(2015) Nanotechnology 26: 271001
MeSH Terms: Drug Carriers, Equipment Design, Models, Chemical, Molecular Imprinting, Nanoparticles, Nanotechnology, Peptide Nucleic Acids, Porosity, Silicon
Show Abstract · Added April 27, 2017
A versatile and scalable method for fabricating shape-engineered nano- and micrometer scale particles from mesoporous silicon (PSi) thin films is presented. This approach, based on the direct imprinting of porous substrates (DIPS) technique, facilitates the generation of particles with arbitrary shape, ranging in minimum dimension from approximately 100 nm to several micrometers, by carrying out high-pressure (>200 MPa) direct imprintation, followed by electrochemical etching of a sub-surface perforation layer and ultrasonication. PSi particles (PSPs) with a variety of geometries have been produced in quantities sufficient for biomedical applications (≫10 μg). Because the stamps can be reused over 150 times, this process is substantially more economical and efficient than the use of electron beam lithography and reactive ion etching for the fabrication of nanometer-scale PSPs directly. The versatility of this fabrication method is demonstrated by loading the DIPS-imprinted PSPs with a therapeutic peptide nucleic acid drug molecule, and by vapor deposition of an Au coating to facilitate the use of PSPs as a photothermal contrast agent.
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2 Members
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9 MeSH Terms
Endosomolytic Nano-Polyplex Platform Technology for Cytosolic Peptide Delivery To Inhibit Pathological Vasoconstriction.
Evans BC, Hocking KM, Kilchrist KV, Wise ES, Brophy CM, Duvall CL
(2015) ACS Nano 9: 5893-907
MeSH Terms: Cells, Cultured, Coronary Vasospasm, Cytosol, Drug Delivery Systems, Humans, Muscle, Smooth, Vascular, Nanostructures, Nanotechnology, Oligopeptides, Polymers, Vasoconstriction
Show Abstract · Added March 14, 2018
A platform technology has been developed and tested for delivery of intracellular-acting peptides through electrostatically complexed nanoparticles, or nano-polyplexes, formulated from an anionic endosomolytic polymer and cationic therapeutic peptides. This delivery platform has been initially tested and optimized for delivery of two unique vasoactive peptides, a phosphomimetic of heat shock protein 20 and an inhibitor of MAPKAP kinase II, to prevent pathological vasoconstriction (i.e., vasospasm) in human vascular tissue. These peptides inhibit vasoconstriction and promote vasorelaxation by modulating actin dynamics in vascular smooth muscle cells. Formulating these peptides into nano-polyplexes significantly enhances peptide uptake and retention, facilitates cytosolic delivery through a pH-dependent endosomal escape mechanism, and enhances peptide bioactivity in vitro as measured by inhibition of F-actin stress fiber formation. In comparison to treatment with the free peptides, which were endowed with cell-penetrating sequences, the nano-polyplexes significantly increased vasorelaxation, inhibited vasoconstriction, and decreased F-actin formation in the human saphenous vein ex vivo. These results suggest that these formulations have significant potential for treatment of conditions such as cerebral vasospasm following subarachnoid hemorrhage. Furthermore, because many therapeutic peptides include cationic cell-penetrating segments, this simple and modular platform technology may have broad applicability as a cost-effective approach for enhancing the efficacy of cytosolically active peptides.
0 Communities
1 Members
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11 MeSH Terms
A new paradigm for treatment of glaucoma.
Galloway RL, Delisi M, Harth EM, Mawn LA
(2014) Annu Int Conf IEEE Eng Med Biol Soc 2014: 6147-50
MeSH Terms: Animals, Blindness, Delayed-Action Preparations, Endoscopy, Equipment Design, Glaucoma, Humans, Magnetic Resonance Imaging, Nanoparticles, Nanostructures, Nanotechnology, Neuroprotective Agents, Phantoms, Imaging, Polyesters, Skull, Swine
Show Abstract · Added February 15, 2016
Glaucoma is the leading irreversible cause of blindness in the world. We are developing a new image-guidance system to deliver a neuroprotective drug in a controlled release nanosponge. The system consists of a magnetically tracked image-guidance system, the nanosponge material and the drug. We have characterized the performance of each aspect in phantoms, animals and ex-vivo human tissue.
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16 MeSH Terms
The microfluidic multitrap nanophysiometer for hematologic cancer cell characterization reveals temporal sensitivity of the calcein-AM efflux assay.
Byrd TF, Hoang LT, Kim EG, Pfister ME, Werner EM, Arndt SE, Chamberlain JW, Hughey JJ, Nguyen BA, Schneibel EJ, Wertz LL, Whitfield JS, Wikswo JP, Seale KT
(2014) Sci Rep 4: 5117
MeSH Terms: Animals, Calcium-Binding Proteins, Cell Separation, Equipment Design, Equipment Failure Analysis, Flow Cytometry, Fluoresceins, Humans, Jurkat Cells, Leukemia, T-Cell, Microfluidic Analytical Techniques, Nanotechnology, Optical Tweezers, Reproducibility of Results, Sensitivity and Specificity, Tissue Array Analysis
Show Abstract · Added February 2, 2015
Cytometric studies utilizing flow cytometry or multi-well culture plate fluorometry are often limited by a deficit in temporal resolution and a lack of single cell consideration. Unfortunately, many cellular processes, including signaling, motility, and molecular transport, occur transiently over relatively short periods of time and at different magnitudes between cells. Here we demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic platform housing an array of cell traps, as an effective tool that can be used to study individual unattached cells over time with precise control over the intercellular microenvironment. We show how the MTNP platform can be used for hematologic cancer cell characterization by measuring single T cell levels of CRAC channel modulation, non-translational motility, and ABC-transporter inhibition via a calcein-AM efflux assay. The transporter data indicate that Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein for over 60 minutes after calcein-AM is removed from the extracellular space.
1 Communities
2 Members
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16 MeSH Terms
Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter.
Mishra S, Verhalen B, Stein RA, Wen PC, Tajkhorshid E, Mchaourab HS
(2014) Elife 3: e02740
MeSH Terms: ATP-Binding Cassette Transporters, Adenosine Triphosphate, Carrier Proteins, Catalytic Domain, Cell Membrane, Cloning, Molecular, Gene Expression Regulation, Hydrolysis, Molecular Dynamics Simulation, Nanotechnology, Nucleotides, Protein Conformation, Protein Multimerization
Show Abstract · Added May 30, 2014
Multidrug ATP binding cassette (ABC) exporters are ubiquitous ABC transporters that extrude cytotoxic molecules across cell membranes. Despite recent progress in structure determination of these transporters, the conformational motion that transduces the energy of ATP hydrolysis to the work of substrate translocation remains undefined. Here, we have investigated the conformational cycle of BmrCD, a representative of the heterodimer family of ABC exporters that have an intrinsically impaired nucleotide binding site. We measured distances between pairs of spin labels monitoring the movement of the nucleotide binding (NBD) and transmembrane domains (TMD). The results expose previously unobserved structural intermediates of the NBDs arising from asymmetric configuration of catalytically inequivalent nucleotide binding sites. The two-state transition of the TMD, from an inward- to an outward-facing conformation, is driven exclusively by ATP hydrolysis. These findings provide direct evidence of divergence in the mechanism of ABC exporters.DOI: http://dx.doi.org/10.7554/eLife.02740.001.
Copyright © 2014, Mishra et al.
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13 MeSH Terms
Cyclooxygenase-2 catalysis and inhibition in lipid bilayer nanodiscs.
Orlando BJ, McDougle DR, Lucido MJ, Eng ET, Graham LA, Schneider C, Stokes DL, Das A, Malkowski MG
(2014) Arch Biochem Biophys 546: 33-40
MeSH Terms: Animals, Biocatalysis, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Enzyme Activation, Humans, Lipid Bilayers, Mice, Models, Molecular, Nanotechnology, Palmitic Acid, Phospholipids, Protein Conformation
Show Abstract · Added January 20, 2015
Cyclooxygenases (COX-1 and COX-2) oxygenate arachidonic acid (AA) to generate prostaglandins. The enzymes associate with one leaflet of the membrane bilayer. We utilized nanodisc technology to investigate the function of human (hu) COX-2 and murine (mu) COX-2 in a lipid bilayer environment. huCOX-2 and muCOX-2 were incorporated into nanodiscs composed of POPC, POPS, DOPC, or DOPS phospholipids. Size-exclusion chromatography and negative stain electron microscopy confirm that a single COX-2 homodimer is incorporated into the nanodisc scaffold. Nanodisc-reconstituted COX-2 exhibited similar kinetic profiles for the oxygenation of AA, eicosapentaenoic acid, and 1-arachidonoyl glycerol compared to those derived using detergent solubilized enzyme. Moreover, changing the phospholipid composition of the nanodisc did not alter the ability of COX-2 to oxygenate AA or to be inhibited by various nonselective NSAIDs or celecoxib. The cyclooxygenase activity of nanodisc-reconstituted COX-2 was reduced by aspirin acetylation and potentiated by the nonsubstrate fatty acid palmitic acid to the same extent as detergent solubilized enzyme, independent of phospholipid composition. The stabilization and maintenance of activity afforded by the incorporation of the enzyme into nanodiscs generates a native-like lipid bilayer environment to pursue studies of COX utilizing solution-based techniques that are otherwise not tractable in the presence of detergents.
Copyright © 2014 Elsevier Inc. All rights reserved.
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13 MeSH Terms
Low-frequency fluctuations of an atomic force microscope cantilever is capable of monitoring nanometer-scale activity of bacteria in real time.
Friedman H, Holt AT, Pham W
(2013) Nanomedicine (Lond) 8: 1910
MeSH Terms: Ampicillin, Anti-Bacterial Agents, Biosensing Techniques, Escherichia coli, Humans, Microscopy, Atomic Force, Nanotechnology, Staphylococcus aureus
Added May 27, 2014
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1 Members
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8 MeSH Terms
Using novel fluorescent decay kinetics near-infrared dyes encased in nanoparticles for imaging.
Friedman H, Holt AT, Pham W
(2013) Nanomedicine (Lond) 8: 1909-10
MeSH Terms: Animals, Nanoparticles, Nanotechnology, Spectroscopy, Near-Infrared
Added May 27, 2014
0 Communities
1 Members
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4 MeSH Terms