Gadolinium-based nanoparticles to improve the hadrontherapy performances.
Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor.


BACKGROUND
Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor.
Institut des Sciences Moléculaires d'Orsay, Université Paris Sud, CNRS, Orsay, France.
Erika
E
Porcel
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS, Villeurbanne, France.
Olivier
O
Tillement
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS, Villeurbanne, France.
François
F
Lux
Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS, Villeurbanne, France.
Pierre
P
Mowat
Photon Factory, Institute of Material Science, High Energy Accelerator Research Organization, Oho 1, Tsukuba, Ibaraki, Japan.
Noriko
N
Usami
Photon Factory, Institute of Material Science, High Energy Accelerator Research Organization, Oho 1, Tsukuba, Ibaraki, Japan.
Katsumi
K
Kobayashi
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Japan.
Yoshiya
Y
Furusawa
Institut des Sciences Moléculaires d'Orsay, Université Paris Sud, CNRS, Orsay, France.
Claude
C
Le Sech
Institut des Sciences Moléculaires d'Orsay, Université Paris Sud, CNRS, Orsay, France.
Sha
S
Li
Institut des Sciences Moléculaires d'Orsay, Université Paris Sud, CNRS, Orsay, France. Electronic address: sandrine.lacombe@u-psud.fr.
Sandrine
S
Lacombe
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005682:Gadolinium / Q000737:chemistry*; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*
D005682:Gadolinium
Gadolinium; Hadrontherapy; Nano-sensitisation; Nanomedicine; Theranostics