title: Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.
abstract: Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Detappe
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Sijumon
authors.initials: S
authors.lastname: Kunjachan
authors.affiliation: Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.affiliation: Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Motto-Ros
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Biancur
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Pascal
authors.initials: P
authors.lastname: Drane
authors.affiliation: Division of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Guieze
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: G Mike
authors.initials: GM
authors.lastname: Makrigiorgos
authors.affiliation: Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Berbeco
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007834:Lasers; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D012822:Silicon Dioxide / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068936:Theranostic Nanomedicine / Q000379:methods
chemical_list: D011838:Radiation-Sensitizing Agents; D012822:Silicon Dioxide; D005682:Gadolinium
keywords: Image-guided radiation therapy; Nanoparticles; Radiosensitizer; Theranostics