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      Imaging intracellular and systemic in vivo gold nanoparticles to enhance radiotherapy

      review-article
      , MSc, PhD 1 , , , BSc, PhD 2 , , BSc, PhD 3
      The British Journal of Radiology
      The British Institute of Radiology.

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          Abstract

          Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both kilo-electron-volt and mega-electron-volt X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumours. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumour samples. Spatially accurate imaging on the nanoscale poses a serious challenge requiring high- or super-resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitizers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our own work, we have used multiphoton excited plasmon resonance imaging to map the AuNP intracellular distribution. The benefits and limitations of this approach will also be discussed in some detail. In some cases, the same “excitation” mechanism as is used in an imaging modality can be harnessed to make it also a part of therapy modality ( e.g. phototherapy)—such examples are discussed in passing as extensions to the imaging modality concerned.

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          Most cited references67

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          Synthesis of thiol-derivatised gold nanoparticles in a two-phase Liquid–Liquid system

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            Über Elementarakte mit zwei Quantensprüngen

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              In vivo three-photon microscopy of subcortical structures within an intact mouse brain

              Two-photon fluorescence microscopy (2PM) 1 enables scientists in various fields including neuroscience 2,3 , embryology 4 , and oncology 5 to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of 2PM within the mouse brain to the cortical layer, and imaging subcortical structures currently requires the removal of overlying brain tissue 3 or the insertion of optical probes 6,7 . Here we demonstrate non-invasive, high resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy (3PM) at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein (RFP)-labeled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher order nonlinear excitation overcomes the limitations of 2PM, enabling biological investigations to take place at greater depth within tissue.
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                Author and article information

                Contributors
                Journal
                Br J Radiol
                Br J Radiol
                bjr
                The British Journal of Radiology
                The British Institute of Radiology.
                0007-1285
                1748-880X
                October 2015
                23 July 2015
                : 88
                : 1054
                : 20150170
                Affiliations
                [ 1 ]Science and Technology Facility Council, Research Complex at Harwell, CLF, Rutherford Appleton Laboratory, Harwell Oxford, Didcot, UK
                [ 2 ]School of Pharmacy, McClay Research Centre, Queen's University Belfast, Belfast, UK
                [ 3 ]School of Mathematics and Physics, Queens University Belfast, Belfast, UK
                Author notes
                Address correspondence to: Professor Stanley Walter Botchway. E-mail: stan.botchway@ 123456stfc.ac.uk
                Article
                15170
                10.1259/bjr.20150170
                4730966
                26118301
                620510c0-26b6-4b38-993a-3b4e492ac6ef
                © 2015 The Authors. Published by the British Institute of Radiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 Unported License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

                History
                : Received on March 1, 2015
                : Revised on June 22, 2015
                : Accepted on June 24, 2015
                Page count
                Figures: 7, Tables: 0, References: 82, Pages: 13
                Categories
                Nanoparticles for Diagnostic Imaging and Radiotherapy Special Feature
                Review Article
                Molecular Imaging

                Radiology & Imaging
                Radiology & Imaging

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