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      Toxicology and clinical potential of nanoparticles

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          Abstract

          Graphical abstract

          Highlights

          ▶ NP toxicity depends on NP characteristics, administered dose and route. ▶ In vitro toxicity results do not easily translate into in vivo toxicity. ▶ Current research lacks a unifying protocol for the toxicological profiling of NPs.

          Summary

          In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports.

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          Most cited references 146

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          Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance.

          Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
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            Is Open Access

            Simple analytical expression for the peak-frequency shifts of plasmonic resonances for sensing

            We derive a closed-form expression that accurately predicts the peak frequency-shift and broadening induced by tiny perturbations of plasmonic nanoresonators without critically relying on repeated electrodynamic simulations of the spectral response of nanoresonator for various locations, sizes or shapes of the perturbing objects. The force of the present approach, in comparison with other approaches of the same kind, is that the derivation is supported by a mathematical formalism based on a rigorous normalization of the resonance modes of nanoresonators consisting of lossy and dispersive materials. Accordingly, accurate predictions are obtained for a large range of nanoparticle shapes and sizes, used in various plasmonic nanosensors, even beyond the quasistatic limit. The expression gives quantitative insight, and combined with an open-source code, provides accurate and fast predictions that are ideally suited for preliminary designs or for interpretation of experimental data. It is also valid for photonic resonators with large mode volumes.
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              Nanoparticle-mediated cellular response is size-dependent.

              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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                Author and article information

                Journal
                Nano Today
                Nano Today
                Nano Today
                Elsevier Ltd
                1748-0132
                1878-044X
                December 2011
                December 2011
                : 6
                : 6
                : 585-607
                Affiliations
                [a ]Centre for Nanotechnology & Regenerative Medicine, UCL Division of Surgery & Interventional Science, University College London, London, UK
                [b ]Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, UK
                [c ]The Davy Faraday Research Laboratory, The Royal Institution of Great Britain, 21 Albemarle Street, London W1S 4BS, UK
                [d ]Royal Free Hampstead NHS Trust Hospital, London, UK
                Author notes
                [* ]Corresponding author at: Department of Physics and Astronomy, University College London, Gower Street, London, WC1E 6BT, UK. Tel.: +44 2074916509. ntk.thanh@ 123456ucl.ac.uk
                Article
                NANTOD211
                10.1016/j.nantod.2011.10.001
                3533686
                23293661
                © 2011 2012 Published by Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

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