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      The Toxic Effects and Mechanisms of CuO and ZnO Nanoparticles

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          Abstract

          Recent nanotechnological advances suggest that metal oxide nanoparticles (NPs) have been expected to be used in various fields, ranging from catalysis and opto-electronic materials to sensors, environmental remediation, and biomedicine. However, the growing use of NPs has led to their release into environment and the toxicity of metal oxide NPs on organisms has become a concern to both the public and scientists. Unfortunately, there are still widespread controversies and ambiguities with respect to the toxic effects and mechanisms of metal oxide NPs. Comprehensive understanding of their toxic effect is necessary to safely expand their use. In this review, we use CuO and ZnO NPs as examples to discuss how key factors such as size, surface characteristics, dissolution, and exposure routes mediate toxic effects, and we describe corresponding mechanisms, including oxidative stress, coordination effects and non-homeostasis effects.

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          PEGylated nanographene oxide for delivery of water-insoluble cancer drugs.

          Zhuang Liu, Joshua T Robinson, Xiaoming Sun … (2008)
          It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
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            Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery.

            Fangqiong Tang, Linlin Li, Dong Chen (2012)
            In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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              Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

              Tian Xia, Michael Kovochich, Monty Liong … (2008)
              Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Materials (Basel)
                Journal ID (iso-abbrev): Materials (Basel)
                Journal ID (publisher-id): materials
                Title: Materials
                Publisher: MDPI
                ISSN (Electronic): 1996-1944
                Publication date (Electronic): 13 December 2012
                Publication date Collection: December 2012
                Volume: 5
                Issue: 12
                Pages: 2850-2871
                Affiliations
                [1 ]Chinese Academy of Science Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, China; E-Mails: changyn@ 123456ihep.ac.cn (Y.-N.C.); zhangmy@ 123456ihep.ac.cn (M.Z.)
                [2 ]School of Life Science, Beijing Institute of Technology, Beijing 100081, China; E-Mail: xialin@ 123456ihep.ac.cn (L.X.)
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mails: xinggm@ 123456ihep.ac.cn (G.X.); zhangjun@ 123456bit.edu.cn (J.Z.); Tel.: +86-10-88235738 (G.X.); +86-10-68915957-085 (J.Z.); Fax: +86-10-88236456 (G.X.)
                Article
                Publisher ID: materials-05-02850
                DOI: 10.3390/ma5122850
                PMC ID: 5449046
                SO-VID: e3d55b1e-65c2-47df-9029-0ab8d4570b11
                Copyright © © 2012 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 license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 01 August 2012
                Date revision received : 24 September 2012
                Date accepted : 03 December 2012
                Categories
                Subject: Review

                Keywords: cuo,zno,nanoparticles,toxic effect,size,solubility,exposure routes,oxidative stress,coordination effects,non-homeostasis effects
                Data availability:
                Keywords: cuo, zno, nanoparticles, toxic effect, size, solubility, exposure routes, oxidative stress, coordination effects, non-homeostasis effects

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