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      Gold nanoparticles for cancer radiotherapy: a review

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          Abstract

          Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak). In addition to ion radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally increase the damaging effect of both photon and ion radiation, when both are applied to the tumour area. Amongst the available nanoparticle systems, gold nanoparticles have become particularly popular due to several advantages: biocompatibility, well-established methods for synthesis in a wide range of sizes, and the possibility of coating of their surface with a large number of different molecules to provide partial control of, for example, surface charge or interaction with serum proteins. This gives a full range of options for design parameter combinations, in which the optimal choice is not always clear, partially due to a lack of understanding of many processes that take place upon irradiation of such complicated systems. In this review, we summarise the mechanisms of action of radiation therapy with photons and ions in the presence and absence of nanoparticles, as well as the influence of some of the core and coating design parameters of nanoparticles on their radiosensitisation capabilities.

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          Most cited references 130

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells.

            We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).
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              Renal clearance of quantum dots.

              The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.
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                Author and article information

                Affiliations
                [1 ]Department of Physical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA UK
                [2 ]Department of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA UK
                [3 ]School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Lisburn Road, Belfast, BT9 7BL UK
                [4 ]Department of Control and Power Engineering, Faculty of Ocean Engineering and Ship Technology, Gdansk University of Technology, 80-233 Gdansk, Poland
                [5 ]MBN Research Center, Altenhöferallee 3, 60438 Frankfurt, Germany
                Contributors
                kaspar.haume@open.ac.uk
                s.rosa@qub.ac.uk
                sophie.grellet@open.ac.uk
                smialek@pg.gda.pl
                k.butterworth@qub.ac.uk
                solovyov@mbnresearch.com
                k.prise@qub.ac.uk
                jon.golding@open.ac.uk
                nigel.mason@open.ac.uk
                Journal
                Cancer Nanotechnol
                Cancer Nanotechnol
                Cancer Nanotechnology
                Springer Vienna (Vienna )
                1868-6958
                1868-6966
                3 November 2016
                3 November 2016
                2016
                : 7
                : 1
                21
                10.1186/s12645-016-0021-x
                5095165
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004963, Seventh Framework Programme;
                Award ID: 608163
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy

                gold nanoparticles, nanomedicine, radiosensitisation

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