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      Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

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          Abstract

          Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed.

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          Nanoparticle-mediated cellular response is size-dependent.

          Wen Jiang, Betty Kim, James T. Rutka … (2008)
          Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2-100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death), 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.
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            In vitro assessments of nanomaterial toxicity.

            Clinton Jones, David Grainger (2009)
            Nanotechnology has grown from a scientific interest to a major industry with both commodity and specialty nanomaterial exposure to global populations and ecosystems. Sub-micron materials are currently used in a wide variety of consumer products and in clinical trials as drug delivery carriers and imaging agents. Due to the expected growth in this field and the increasing public exposure to nanomaterials, both from intentional administration and inadvertent contact, improved characterization and reliable toxicity screening tools are required for new and existing nanomaterials. This review discusses current methodologies used to assess nanomaterial physicochemical properties and their in vitro effects. Current methods lack the desired sensitivity, reliability, correlation and sophistication to provide more than limited, often equivocal, pieces of the overall nanomaterial performance parameter space, particularly in realistic physiological or environmental models containing cells, proteins and solutes. Therefore, improved physicochemical nanomaterial assays are needed to provide accurate exposure risk assessments and genuine predictions of in vivo behavior and therapeutic value. Simpler model nanomaterial systems in buffer do not accurately duplicate this complexity or predict in vivo behavior. A diverse portfolio of complementary material characterization tools and bioassays are required to validate nanomaterial properties in physiology.
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              Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines.

              Marina A. Dobrovolskaia, Scott E. McNeil (2013)
              Preclinical characterization of novel nanotechnology-based formulations is often challenged by physicochemical characteristics, sterility/sterilization issues, safety and efficacy. Such challenges are not unique to nanomedicine, as they are common in the development of small and macromolecular drugs. However, due to the lack of a general consensus on critical characterization parameters, a shortage of harmonized protocols to support testing, and the vast variety of engineered nanomaterials, the translation of nanomedicines into clinic is particularly complex. Understanding the immune compatibility of nanoformulations has been identified as one of the important factors in (pre)clinical development and requires reliable in vitro and in vivo immunotoxicity tests. The generally low sensitivity of standard in vivo toxicity tests to immunotoxicities, inter-species variability in the structure and function of the immune system, high costs and relatively low throughput of in vivo tests, and ethical concerns about animal use underscore the need for trustworthy in vitro assays. Here, we consider the correlation (or lack thereof) between in vitro and in vivo immunotoxicity tests as a mean to identify useful in vitro assays. We review literature examples and case studies from the experience of the NCI Nanotechnology Characterization Lab, and highlight assays where predictability has been demonstrated for a variety of nanomaterials and assays with high potential for predictability in vivo.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 18 November 2017
                Publication date Collection: November 2017
                Volume: 18
                Issue: 11
                Electronic Location Identifier: 2454
                Affiliations
                [1 ]SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway; vu.nakstad@ 123456sintef.no (V.T.N.); geir.klinkenberg@ 123456sintef.no (G.K.); havard.sletta@ 123456sintef.no (H.S.); ruth.b.schmid@ 123456sintef.no (R.S.); annerein.hatletveit@ 123456sintef.no (A.R.H.); ane.marit.wagbo@ 123456sintef.no (A.M.W.); yrr.morch@ 123456sintef.no (Ý.M.)
                [2 ]Department of Physics, Norwegian University of Science and Technology, Høgskoleringen 5, 7491 Trondheim, Norway
                [3 ]Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital—The Norwegian Radium Hospital, 0379 Oslo, Norway; Tore-Geir.Iversen@ 123456rr-research.no (T.-G.I.); tore.skotland@ 123456rr-research.no (T.S.); kirsten.sandvig@ 123456ibv.uio.no (K.S.)
                [4 ]Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway
                [5 ]Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 8905 MH, 7491 Trondheim, Norway; anders.sundan@ 123456ntnu.no
                [6 ]Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway
                Author notes
                [* ]Correspondence: einar.sulheim@ 123456ntnu.no ; Tel.: +47-73593478
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: ijms-18-02454
                DOI: 10.3390/ijms18112454
                PMC ID: 5713421
                PubMed ID: 29156588
                SO-VID: ae631d4b-d670-4570-af4c-01efb57e0bad
                Copyright © © 2017 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 : 17 October 2017
                Date accepted : 15 November 2017
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: nanoparticles,paca,cytotoxicity,nanotoxicology,high-throughput screening
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: nanoparticles, paca, cytotoxicity, nanotoxicology, high-throughput screening

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