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  1. Article ; Online: L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles.

    Gonzalez-Carter, Daniel A / Ong, Zhan Yuin / McGilvery, Catriona M / Dunlop, Iain E / Dexter, David T / Porter, Alexandra E

    Nanomedicine : nanotechnology, biology, and medicine

    2018  Volume 15, Issue 1, Page(s) 1–11

    Abstract: The blood-brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB ... ...

    Abstract The blood-brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB to deliver therapies into the brain. The drug L-DOPA efficiently and specifically crosses the BBB via the large neutral amino acid transporter (LAT)-1 protein to enter the brain. Thus, we synthesized L-DOPA-functionalized multi-branched nanoflower-like gold nanoparticles (L-DOPA-AuNFs) using a seed-mediated method involving catechols as a direct reducing-cum-capping agent, and examined their ability to cross the BBB to act as brain-penetrating nanovehicles. We show that L-DOPA-AuNFs efficiently penetrate the BBB compared to similarly sized and shaped AuNFs functionalized with a non-targeting ligand. Furthermore, we show that L-DOPA-AuNFs are efficiently internalized by brain macrophages without inducing inflammation. These results demonstrate the application of L-DOPA-AuNFs as a non-inflammatory BBB-penetrating nanovehicle to efficiently deliver therapies into the brain.
    MeSH term(s) Animals ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; Cells, Cultured ; Dopamine Agents/administration & dosage ; Dopamine Agents/chemistry ; Drug Delivery Systems ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Gold/chemistry ; Humans ; Levodopa/administration & dosage ; Levodopa/chemistry ; Male ; Metal Nanoparticles/administration & dosage ; Metal Nanoparticles/chemistry ; Rats ; Rats, Wistar
    Chemical Substances Dopamine Agents ; Levodopa (46627O600J) ; Gold (7440-57-5)
    Language English
    Publishing date 2018-09-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2183417-9
    ISSN 1549-9642 ; 1549-9634
    ISSN (online) 1549-9642
    ISSN 1549-9634
    DOI 10.1016/j.nano.2018.08.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Towards multiplexed near-infrared cellular imaging using gold nanostar arrays with tunable fluorescence enhancement.

    Theodorou, Ioannis G / Ruenraroengsak, Pakatip / Gonzalez-Carter, Daniel A / Jiang, Qianfan / Yagüe, Ernesto / Aboagye, Eric O / Coombes, R Charles / Porter, Alexandra E / Ryan, Mary P / Xie, Fang

    Nanoscale

    2019  Volume 11, Issue 4, Page(s) 2079–2088

    Abstract: Sensitive detection of disease biomarkers expressed by human cells is critical to the development of novel diagnostic and therapeutic methods. Here we report that plasmonic arrays based on gold nanostar (AuNS) monolayers enable up to 19-fold fluorescence ...

    Abstract Sensitive detection of disease biomarkers expressed by human cells is critical to the development of novel diagnostic and therapeutic methods. Here we report that plasmonic arrays based on gold nanostar (AuNS) monolayers enable up to 19-fold fluorescence enhancement for cellular imaging in the near-infrared (NIR) biological window, allowing the application of low quantum yield fluorophores for sensitive cellular imaging. The high fluorescence enhancement together with low autofluorescence interference in this wavelength range enable higher signal-to-noise ratio compared to other diagnostic modalities. Using AuNSs of different geometries and therefore controllable electric field enhancement, cellular imaging with tunable enhancement factors is achieved, which may be useful for the development of multicolour and multiplexed platforms for a panel of biomarkers, allowing to distinguish different subcell populations at the single cell level. Finally, the uptake of AuNSs within HeLa cells and their high biocompatibility, pave the way for novel high-performance in vitro and in vivo diagnostic platforms.
    Language English
    Publishing date 2019-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2515664-0
    ISSN 2040-3372 ; 2040-3364
    ISSN (online) 2040-3372
    ISSN 2040-3364
    DOI 10.1039/c8nr09409h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H

    Gonzalez-Carter, Daniel A / Leo, Bey Fen / Ruenraroengsak, Pakatip / Chen, Shu / Goode, Angela E / Theodorou, Ioannis G / Chung, Kian Fan / Carzaniga, Raffaella / Shaffer, Milo S P / Dexter, David T / Ryan, Mary P / Porter, Alexandra E

    Scientific reports

    2017  Volume 7, Page(s) 42871

    Abstract: Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in ... ...

    Abstract Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson's disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag
    MeSH term(s) Animals ; Cell Line ; Cell Survival/drug effects ; Cystathionine gamma-Lyase/metabolism ; Encephalitis/drug therapy ; Encephalitis/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; Hydrogen Sulfide/metabolism ; Lipopolysaccharides/adverse effects ; Metal Nanoparticles/chemistry ; Mice ; Microglia/cytology ; Microglia/drug effects ; Microglia/metabolism ; Models, Biological ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Neurotoxicity Syndromes/drug therapy ; Neurotoxicity Syndromes/metabolism ; Oxidative Stress/drug effects ; Silver/chemistry ; Silver/pharmacology
    Chemical Substances Lipopolysaccharides ; Silver (3M4G523W1G) ; Cystathionine gamma-Lyase (EC 4.4.1.1) ; Hydrogen Sulfide (YY9FVM7NSN)
    Language English
    Publishing date 2017-03-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep42871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells.

    Goode, Angela E / Gonzalez Carter, Daniel A / Motskin, Michael / Pienaar, Ilse S / Chen, Shu / Hu, Sheng / Ruenraroengsak, Pakatip / Ryan, Mary P / Shaffer, Milo S P / Dexter, David T / Porter, Alexandra E

    Biomaterials

    2015  Volume 70, Page(s) 57–70

    Abstract: Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation ... ...

    Abstract Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation may have different bioreactivities and propensities to aggregate in the extracellular environment, and both individualised and aggregated MWNTs may be expected to be found in the brain. Before practical application, it is vital to understand how both aggregates and individual MWNTs will interact with local phagocytic immune cells, the microglia, and ultimately to determine their biopersistence in the brain. The processing of extra- and intracellular MWNTs (both pristine and when acid oxidised) by microglia was characterised across multiple length scales by correlating a range of dynamic, quantitative and multi-scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion beam scanning electron microscopy and transmission electron microscopy. Dynamic, live cell imaging revealed the ability of microglia to break apart and internalise micron-sized extracellular agglomerates of acid oxidised MWNTs, but not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound to, microglia was quantified as a function of time. Neither the significant uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected microglial viability, pro-inflammatory cytokine release or nitric oxide production. However, after 24 h exposure to pristine MWNTs, a significant increase in the production of reactive oxygen species was observed. Small aggregates and individualised oxidised MWNTs were present in the cytoplasm and vesicles, including within multilaminar bodies, after 72 h. Some evidence of morphological damage to oxidised MWNT structure was observed including highly disordered graphitic structures, suggesting possible biodegradation. This work demonstrates the utility of dynamic, quantitative and multi-scale techniques in understanding the different cellular processing routes of functionalised nanomaterials. This correlative approach has wide implications for assessing the biopersistence of MWNT aggregates elsewhere in the body, in particular their interaction with macrophages in the lung.
    MeSH term(s) Animals ; Cell Survival/drug effects ; Cytokines/biosynthesis ; Endocytosis/drug effects ; Extracellular Space/chemistry ; Imaging, Three-Dimensional/methods ; Intracellular Space/chemistry ; Mice ; Microglia/cytology ; Microglia/drug effects ; Microglia/ultrastructure ; Nanotubes, Carbon/toxicity ; Nanotubes, Carbon/ultrastructure ; Oxidation-Reduction ; Spectrophotometry, Ultraviolet
    Chemical Substances Cytokines ; Nanotubes, Carbon
    Language English
    Publishing date 2015-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.08.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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