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      Nervous System Injury in Response to Contact With Environmental, Engineered and Planetary Micro- and Nano-Sized Particles

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          Abstract

          Nerve cells take a special place among other cells in organisms because of their unique function mechanism. The plasma membrane of nerve cells from the one hand performs a classical barrier function, thereby being foremost targeted during contact with micro- and nano-sized particles, and from the other hand it is very intensively involved in nerve signal transmission, i.e., depolarization-induced calcium-dependent compound exocytosis realized via vesicle fusion following by their retrieval and calcium-independent permanent neurotransmitter turnover via plasma membrane neurotransmitter transporters that utilize Na +/K + electrochemical gradient as a driving force. Worldwide traveling air pollution particulate matter is now considered as a possible trigger factor for the development of a variety of neuropathologies. Micro- and nano-sized particles can reach the central nervous system during inhalation avoiding the blood–brain barrier, thereby making synaptic neurotransmission extremely sensitive to their influence. Neurosafety of environmental, engineered and planetary particles is difficult to predict because they possess other features as compared to bulk materials from which the particles are composed of. The capability of the particles to absorb heavy metals and organic neurotoxic molecules from the environment, and moreover, spontaneously interact with proteins and lipids in organisms and form biomolecular corona can considerably change the particles‘ features. The absorption capability occasionally makes them worldwide traveling particulate carriers for delivery of environmental neurotoxic compounds to the brain. Discrepancy of the experimental data on neurotoxicity assessment of micro- and nano-sized particles can be associated with a variability of systems, in which neurotoxicity was analyzed and where protein components of the incubation media forming particle biocorona can significantly distort and even eliminate factual particle effects. Specific synaptic mechanisms potentially targeted by environmental, engineered and planetary particles, general principles of particle neurosafety and its failure were discussed. Particle neurotoxic potential depends on their composition, size, shape, surface properties, stability in organisms and environment, capability to absorb neurotoxic compounds, form dust and interrelate with different biomolecules. Changes in these parameters can break primary particle neurosafety.

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          Most cited references121

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          Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

          It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.
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            Intranasal delivery of biologics to the central nervous system.

            Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Time evolution of the nanoparticle protein corona.

              In this work, we explore the formation of the protein corona after exposure of metallic Au nanoparticles (NPs), with sizes ranging from 4 to 40 nm, to cell culture media containing 10% of fetal bovine serum. Under in vitro cell culture conditions, zeta potential measurements, UV-vis spectroscopy, dynamic light scattering and transmission electron microscope analysis were used to monitor the time evolution of the inorganic NP-protein corona formation and to characterize the stability of the NPs and their surface state at every stage of the experiment. As expected, the red-shift of the surface plasmon resonance peak, as well as the drop of surface charge and the increase of the hydrodynamic diameter indicated the conjugation of proteins to NPs. Remarkably, an evolution from a loosely attached toward an irreversible attached protein corona over time was observed. Mass spectrometry of the digested protein corona revealed albumin as the most abundant component which suggests an improved biocompatibility.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                26 June 2018
                2018
                : 9
                : 728
                Affiliations
                Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine , Kiev, Ukraine
                Author notes

                Edited by: Dieter Blottner, Charité Universitätsmedizin Berlin, Germany

                Reviewed by: Michele Salanova, Charité Universitätsmedizin Berlin, Germany; Elena S. Tomilovskaya, Institute of Biomedical Problems (RAS), Russia; Stephane Besnard, Institut National de la Santé et de la Recherche Médicale (INSERM), France

                This article was submitted to Environmental, Aviation and Space Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.00728
                6028719
                29997517
                511d8782-8dfb-4df2-8483-bc729c1ed10d
                Copyright © 2018 Borisova.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 February 2018
                : 25 May 2018
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 146, Pages: 16, Words: 0
                Funding
                Funded by: National Academy of Sciences of Ukraine 10.13039/501100004742
                Award ID: Programs: “Molecular and cellular biotechnologies for medicine, industry, and agriculture”; “Scientific Space Research”
                Funded by: Horizon 2020 10.13039/501100007601
                Award ID: ERA-PLANET Strands 1 & 3
                Categories
                Physiology
                Review

                Anatomy & Physiology
                micro- and nano-sized particles,air pollution particulate matter,particle biocorona,nervous system,neurosafety

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