title: Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization.
abstract: The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: jschuemann@mgh.harvard.edu.
authors.forename: Jan
authors.initials: J
authors.lastname: Schuemann
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ross
authors.initials: R
authors.lastname: Berbeco
authors.affiliation: Department of Physics, Ryerson University, Toronto, Ontario, Canada.
authors.forename: Devika B
authors.initials: DB
authors.lastname: Chithrani
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts; Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts; Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D001776:Blood Circulation Time; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D009010:Monte Carlo Method; D009369:Neoplasms / Q000098:blood supply / Q000532:radiotherapy*; D010316:Particle Size; D017785:Photons / Q000627:therapeutic use; D061766:Proton Therapy; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013499:Surface Properties
chemical_list: D011838:Radiation-Sensitizing Agents; D006046:Gold