期刊
ADVANCED SCIENCE
卷 7, 期 20, 页码 -出版社
WILEY
DOI: 10.1002/advs.202001675
关键词
glioblastoma; nanoscintillators; radiation dose-enhancement; synchrotron radiation; X-ray-induced photodynamic therapy
资金
- Fondation pour la Recherche Medicale [ARF20170938739]
- Region Auvergne Rhone-Alpes through the Pack Ambition Recherche program (NEPTUNE project)
- Ligue Contre le Cancer Foundation [R19ELLEAUME]
- LABEX PRIMES of Universite de Lyon, within the program Investissements d'Avenir [ANR-11-LABX-0063, ANR-11-ISEX-0007]
- Rotary Club Association through the program Jetons Cancer
- project CALIPSOplus under EU Framework Program for Research and Innovation HORIZON 2020 [730872]
- French program Investissement d'Avenir by the ANR [ANR-11-INBS-0006]
To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down-convert X-rays into photons with energies ranging from UV to near-infrared. During radiotherapy, these scintillating properties amplify radiation-induced damage by UV-C emission or photodynamic effects. Additionally, nanoscintillators that contain high-Z elements are likely to induce another, currently unexplored effect: radiation dose-enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X-rays by high-Z elements compared to tissues, resulting in increased production of tissue-damaging photo- and Auger electrons. In this study, Geant4 simulations reveal that rare-earth composite LaF3:Ce nanoscintillators effectively generate photo- and Auger-electrons upon orthovoltage X-rays. 3D spatially resolved X-ray fluorescence microtomography shows that LaF3:Ce highly concentrates in microtumors and enhances radiotherapy in an X-ray energy-dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF3:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose-enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据