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      Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity

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          Abstract

          Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

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          Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts.

          Martin Lundqvist, Johannes Stigler, Giuliano Elia … (2008)
          Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the "protein corona" that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived ("hard") protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.
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            Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes.

            B Devika Chithrani, Warren C W Chan (2007)
            We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require "controlling" NP accumulation rate. These studies will also have implications in determining nanotoxicity.
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              Probing the Cytotoxicity of Semiconductor Quantum Dots

              Austin M. Derfus, Warren C W Chan, Sangeeta N. Bhatia (2004)
              With their bright, photostable fluorescence, semiconductor quantum dots show promise as alternatives to organic dyes for biological labeling. Questions about their potential cytotoxicity, however, remain unanswered. While cytotoxicity of bulk cadmium selenide (CdSe) is well documented, a number of groups have suggested that CdSe QDs are cytocompatible, at least with some immortalized cell lines. Using primary hepatocytes as a liver model, we found that CdSe-core QDs were indeed acutely toxic under certain conditions. Specifically, we found that the cytotoxicity of QDs was modulated by processing parameters during synthesis, exposure to ultraviolet light, and surface coatings. Our data further suggests that cytotoxicity correlates with the liberation of free Cd2+ ions due to deterioration of the CdSe lattice. When appropriately coated, CdSe-core QDs can be rendered non-toxic and used to track cell migration and reorganization in vitro. Our results inform design criteria for the use of QDs in vitro and especially in vivo where deterioration over time may occur.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nanomaterials (Basel)
                Journal ID (iso-abbrev): Nanomaterials (Basel)
                Journal ID (publisher-id): nanomaterials
                Title: Nanomaterials
                Publisher: MDPI
                ISSN (Electronic): 2079-4991
                Publication date (Electronic): 21 August 2018
                Publication date Collection: September 2018
                Volume: 8
                Issue: 9
                Electronic Location Identifier: 634
                Affiliations
                [1 ]Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran P.O. Box 1449614525, Iran; Maa.biology92@ 123456gmail.com
                [2 ]Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran P.O Box 14965/161, Iran; a-moosavi@ 123456nigeb.ac.ir
                [3 ]Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran P.O. Box 13145-158, Iran; m_rahmati@ 123456sina.tums.ac.ir
                [4 ]Department of Nanotechnology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branches, Islamic Azad University of Tehran, Tehran P.O. Box 1916893813, Iran; Falahati@ 123456ibb.ut.ac.ir
                [5 ]Department of Midwifery and Reproductive Health, Faculty of Nursing and Midwifery, Abadan School of Medical Sciences, Abadan P.O. Box 517, Iran; Mm59m@ 123456yahoo.com
                [6 ]Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman P.O. Box 1355576169, Iran
                [7 ]Neuroscience Research Center, Institute of Neuropharmacology, and Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman P.O. Box 7616911319, Iran; alimandegary@ 123456yahoo.com
                [8 ]School of Medicine, International Branch, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
                [9 ]Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University in Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic
                Author notes
                [* ]Correspondence: saranazjangjoo@ 123456gmail.com (S.J.); reza.mn2008@ 123456gmail.com (R.M.); varma.rajender@ 123456epa.gov (R.S.V.); Tel.: +98-93-7839-2628 (S.J.); +98-91-3247-9160 (R.M.); +1-513-487-2701 (R.S.V.); Fax: +98-71-3235-9317 (S.J.); +98-34-3132-5003 (R.M.); +1-513-569-7677 (R.S.V.)
                Author information
                https://orcid.org/0000-0002-4154-7788
                https://orcid.org/0000-0002-1065-9349
                https://orcid.org/0000-0001-9731-6228
                Article
                Publisher ID: nanomaterials-08-00634
                DOI: 10.3390/nano8090634
                PMC ID: 6164883
                PubMed ID: 30134524
                SO-VID: 5e3a9a93-e136-40c0-9a00-73cb08d091f8
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 01 August 2018
                Date accepted : 15 August 2018
                Categories
                Subject: Review

                Keywords: nanoparticles,toxicological effects,organ-specific effects
                Data availability:
                Keywords: nanoparticles, toxicological effects, organ-specific effects

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