Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy

Sijumon Kunjachan, Alexandre Detappe, Rajiv Kumar, Thomas Ireland, Lisa Cameron, Douglas E. Biancur, Vincent Motto-Ros, Lucie Sancey, Srinivas Sridhar, G. Mike Makrigiorgos, Ross I. Berbeco

Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, United States
Institut Lumière Matière, Université Claude Bernard Lyon1-CNRS, Université de Lyon, 69007 Lyon, France
Nanomedicine Science and Technology Center and Department of Physics, Northeastern University, Boston, Massachusetts 02115, United States
LA-ICP-MS and ICP-ES Laboratories, Boston University, Boston, Massachusetts 02215, United States
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States

More than 50% of all cancer patients receive radiation therapy. The clinical delivery of curative radiation dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting strategy using vessel-targeted-radiosensitizing gold nanoparticles and conformal-image guided radiation therapy to specifically amplify damage in the tumor neoendothelium. The resulting tumor vascular disruption substantially improved the therapeutic outcome and subsidized the radiation/nanoparticle toxicity, extending its utility to intransigent or nonresectable tumors that barely respond to standard therapies.

KEYWORDS: Gold nanoparticles, image-guided radiation therapy, endothelial radiation damage, tumor vascular disruption

DOI: 10.1021/acs.nanolett.5b03073 NANO LETTERS XXXX, XXX, XXX−XXX