Radiosensitization Effect of AGuIX, a Gadolinium-Based Nanoparticle, in Nonsmall Cell Lung Cancer
Radiosensitization Effect of AGuIX, a Gadolinium-Based Nanoparticle, in Nonsmall Cell Lung Cancer
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钆基纳米颗粒 AGuIX 对非小细胞肺癌的放射增敏作用
DOI：
10.1021/acsami.0c16548
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发表时间：
2020-12-23
影响因子：
9.5
通讯作者：
Tillement, Olivier
中科院分区：
文献类型：
--
作者：
Du, Yanan;Sun, Hao;Tillement, Olivier
放射治疗是癌症患者的主要治疗方法。放射治疗中的一个主要问题是某些肿瘤的辐射抵抗，例如人类非小细胞肺癌。然而，提供给肿瘤的辐射剂量往往受到对周围健康组织的附带损害的可能性的限制。一种新的、高效的格拉基纳米粒子，AGuIX，最近被开发出来用于磁共振成像引导放射治疗，并被证明是一种有效的放射增敏剂。AGuIX纳米粒子的放大辐射效应似乎是由于发射低能光电子和俄歇电子相互作用造成的。我们证明，AGuIX纳米颗粒加剧了辐射诱导的H1299非小细胞肺癌细胞系的DNA双链断裂损伤和DNA修复。此外，在H1299小鼠异种移植模型中，我们观察到在放射治疗下，AGuIX纳米颗粒在肿瘤细胞损伤和生长抑制方面有显著改善。本研究为进一步研究AGuIX纳米粒子的放射增敏机理奠定了基础，为AGuIX纳米粒子作为放射增敏药物的应用提供了科学依据。
Radiotherapy is the main treatment for cancer patients. A major concern in radiotherapy is the radiation resistance of some tumors, such as human nonsmall cell lung cancer. However, the radiation dose delivered to the tumors is often limited by the possibility of collateral damage to surrounding healthy tissues. A new and efficient gadolinium-based nanoparticle, AGuIX, has recently been developed for magnetic resonance imaging-guided radiotherapy and has been proven to act as an efficient radiosensitizer. The amplified radiation effects of AGuIX nanoparticles appear to be due to the emission of low-energy photoelectrons and Auger electron interactions. We demonstrated that AGuIX nanoparticles exacerbated radiation-induced DNA double-strand break damage and reduced DNA repair in the H1299 nonsmall cell lung cancer cell line. Furthermore, we observed a significant improvement in tumor cell damage and growth suppression, under radiation therapy, with the AGuIX nanoparticles in a H1299 mouse xenograft model. This study paves the way for research into the radiosensitization mechanism of AGuIX nanoparticles and provides a scientific basis for the use of AGuIX nanoparticles as radiosensitizing drugs.