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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Would Colloidal Gold Nanocarriers Present An Effective Diagnosis Or Treatment For Ischemic Stroke?

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          Abstract

          Introduction

          This study was conducted to evaluate OX26-PEG-coated gold nanoparticles (GNPs) (OX26@GNPs) as a novel targeted nanoparticulate system on cell survival after ischemic stroke.

          Materials and methods

          Dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM) were performed to characterize the OX26@GNPs. The effect of OX26@GNPs on infarct volume, neuronal loss, and necroptosis was evaluated 24 h after reperfusion using 2, 3,5-Triphenyltetrazolium chloride (TTC) staining, Nissl staining and Western blot assay, respectively.

          Results

          Conjugation of OX26-PEG to the surface of the 25 nm colloidal gold particles increased their size to 32±2 nm, while a zeta potential change of −40.4 to 3.40 mV remarkably increased the stability of the nanoparticles. Most importantly, OX26@GNPs significantly increased the infarcted brain tissue, while bare GNPs and PEGylated GNPs had no effect on the infarct volume. However, our results indicated an extension of necroptotic cell death, followed by cell membrane damage.

          Conclusion

          Collectively, our results showed that the presently formulated OX26@GNPs are not suitable nanocarriers nor contrast agents under oxidative stress for the diagnosis and treatment of ischemic stroke. Moreover, our findings suggest that the cytotoxicity of GNPs in the brain is significantly associated with their surface charge.

          Most cited references45

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          A simple method for clinical assay of superoxide dismutase.

          This assay for superoxide dismutase (SOD, EC 1.15.1.1) activity involves inhibition of nitroblue tetrazolium reduction, with xanthine-xanthine oxidase used as a superoxide generator. By using a reaction terminator, we can determine 40 samples within 55 min. One unit of activity of pure bovine liver Cu,ZnSOD and chicken liver MnSOD was expressed by 30 ng and 500 ng of protein, respectively. The mean concentrations of Cu,ZnSOD as measured by this method in blood from normal adults were 242 (SEM 4) mg/L in erythrocytes, 548 (SEM 20) micrograms/L in serum, and 173 (SEM 11) micrograms/L in plasma. The Cu,ZnSOD concentrations in serum and plasma of patients with cancer of the large intestine tended to be less and greater than these values, respectively, but not statistically significantly so.
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            Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

            The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.
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              Understanding the role of surface charges in cellular adsorption versus internalization by selectively removing gold nanoparticles on the cell surface with a I2/KI etchant.

              This Letter presents a new method for differentiating the Au nanospheres attached to the cell surface from those being internalized into the cells. We introduced an etching solution based on I2 and KI that can selectively dissolve the Au nanospheres on the cell surface within a short period of time. The advantage of this etchant is its low toxicity to the cells because it is capable of etching away a relatively large amount of Au nanospheres at a low molar concentration. By combining with quantitative elemental analysis, we found that the deposition of Au nanospheres on the surface of cancer cells was highly dependent on the sign of surface charges on the Au nanospheres. In addition, by fitting the uptake data with a kinetic model, we were able to derive the overall and internalization rate constants for Au nanospheres and both of them were found to be governed by the surface charges on Au nanospheres.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                IJN
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                07 October 2019
                2019
                : 14
                : 8013-8031
                Affiliations
                [1 ]Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences , Tehran, Iran
                [2 ]Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences , Tehran, Iran
                [3 ]Department of Chemical Engineering, Northeastern University , Boston, MA, USA
                [4 ]Anesthesia Department, Faculty of Medicine, Iran University of Medical Sciences , Tehran, Iran
                [5 ]Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences , Tehran, Iran
                [6 ]Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences , Tabriz, Iran
                [7 ]Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences , Tehran, Iran
                Author notes
                Correspondence: Thomas J Webster Department of Chemical Engineering, Northeastern University , Boston, MA, USA Email th.webster@neu.edu
                Hamidreza Pazoki-Toroudi Physiology Research Center and Department of Physiology, Iran University of Medical Sciences , P.O. Box 14515-763, Tehran, IranFax +98-21-88675760 Email pazoki49@gmail.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-9092-5642
                http://orcid.org/0000-0003-3958-5002
                http://orcid.org/0000-0002-9742-0292
                http://orcid.org/0000-0001-9592-115X
                http://orcid.org/0000-0001-7868-456X
                Article
                210035
                10.2147/IJN.S210035
                6789974
                31632015
                c20ff587-faea-48bd-a602-68666c72ec44
                © 2019 Amani et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 26 March 2019
                : 17 September 2019
                Page count
                Figures: 10, Tables: 2, References: 64, Pages: 19
                Categories
                Original Research

                Molecular medicine
                targeted delivery,gold nanoparticles,necroptosis,surface charge,oxidative stress,cytotoxicity

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