Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Resonance-Computed Tomography Image Guided Radiation Therapy.
Selective killing of cancer cells while minimizing damage to healthy tissues is the goal of clinical radiation therapy. This therapeutic ratio can be improved by image-guided radiation delivery and selective radiosensitization of cancer cells. Here, we have designed and tested a novel trimodal theranostic nanoparticle made of bismuth and gadolinium for on-site radiosensitization and image contrast enhancement to improve the efficacy and accuracy of radiation therapy. We demonstrate in vivo magnetic resonance (MR), computed tomography (CT) contrast enhancement, and tumor suppression with prolonged survival in a non-small cell lung carcinoma model during clinical radiation therapy. Histological studies show minimal off-target toxicities due to the nanoparticles or radiation. By mimicking existing clinical workflows, we show that the bismuth-gadolinium nanoparticles are highly compatible with current CT-guided radiation therapy and emerging MR-guided approaches. This study reports the first in vivo proof-of-principle for image-guided radiation therapy with a new class of theranostic nanoparticles.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02115, United States.|Department of Radiation Oncology, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.|Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS UMR5306 , 69622 Villeurbanne, France.
Alexandre
0000-0001-9364-1621
A
Detappe
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS UMR5306 , 69622 Villeurbanne, France.
Eloise
E
Thomas
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Mark W
0000-0002-4917-7187
MW
Tibbitt
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02115, United States.|Department of Radiation Oncology, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.
Sijumon
0000-0002-5359-9219
S
Kunjachan
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute at Harvard and MIT , Boston, Massachusetts 02142, United States.
Oksana
O
Zavidij
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02115, United States.
Nishita
N
Parnandi
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02115, United States.
Elizaveta
E
Reznichenko
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS UMR5306 , 69622 Villeurbanne, France.
François
F
Lux
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS UMR5306 , 69622 Villeurbanne, France.
Olivier
O
Tillement
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts 02115, United States.|Department of Radiation Oncology, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.
Ross
R
Berbeco
D000072283:A549 Cells; D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001729:Bismuth / Q000737:chemistry / Q000627:therapeutic use*; D003287:Contrast Media / Q000737:chemistry / Q000627:therapeutic use*; D005682:Gadolinium / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D061089:Radiotherapy, Image-Guided; D012822:Silicon Dioxide / Q000737:chemistry / Q000627:therapeutic use*; D000068936:Theranostic Nanomedicine; D014057:Tomography, X-Ray Computed
D003287:Contrast Media; D012822:Silicon Dioxide; D005682:Gadolinium; D001729:Bismuth
Radiosentization; bismuth; image-guided radiation therapy; nanomedicine; nanoparticle