X-Ray-Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4:Ce3+ Scintillators and their Applications for Radiosensitization
X-Ray-Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4:Ce3+ Scintillators and their Applications for Radiosensitization
复制标题
基于纳米 LiLuF4:Ce3 闪烁体的 X 射线控制生成过氧亚硝酸盐及其在放射增敏中的应用
DOI：
10.1002/adma.201804046
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发表时间：
2018-10-25
影响因子：
29.4
通讯作者：
Zhao, Yuliang
中科院分区：
文献类型：
--
作者：
Du, Zhen;Zhang, Xiao;Zhao, Yuliang
过氧亚硝酸盐（ONOO-）是由一氧化氮（NO）和超氧化物（O-2（-中心点））衍生的反应产物，是一种有效的氧化和硝化剂，调节复杂的生物过程并促进细胞死亡。因此，可以预期，在肿瘤中过量产生ONOO-可以是癌症治疗的有效方法。本文报道了一种基于放射性纳米颗粒（SCNP）和UV响应性NO供体金雀花素黑盐的多功能X射线控制的ONOO生成平台，从而说明了它们在增强放射治疗效果中的应用机制。由于SCNPs的辐射发光和高X射线吸收特性，纳米复合材料在X射线激发下可以同时产生NO和O-2（-中心点）。这种NO和O-2（-中心点）的同时释放确保了肿瘤中ONOO-的有效X射线控制生成。同时，应用X射线作为激发源可以在该纳米治疗平台中获得更好的穿透深度并诱导放射治疗。研究发现，X射线控制的ONOO产生平台可以通过直接损伤DNA，下调DNA修复酶的表达，克服放疗中缺氧相关的抵抗，有效地提高放疗效率。因此，这种基于SCNP的平台可以提供一种新的ONOO和放射治疗的组合策略，以改善癌症治疗。
Peroxynitrite (ONOO-), the reaction product derived from nitric oxide (NO) and superoxide (O-2(-center dot)), is a potent oxidizing and nitrating agent that modulates complex biological processes and promotes cell death. Therefore, it can be expected that the overproduction of ONOO- in tumors can be an efficient approach in cancer therapy. Herein, a multifunctional X-ray-controlled ONOO- generation platform based on scintillating nanoparticles (SCNPs) and UV-responsive NO donors Roussin's black salt is reported, and consequently the mechanism of their application in enhanced therapeutic efficacy of radiotherapy is illustrated. Attributed to the radioluminescence and high X-ray-absorbing property of SCNPs, the nanocomposite can produce NO and O-2(-center dot) simultaneously when excited by X-ray irradiation. Such simultaneous release of NO and O-2(-center dot) ensures the efficient X-ray-controlled generation of ONOO- in tumors. Meanwhile, the application of X-rays as the excitation source can achieve better penetration depth and induce radiotherapy in this nanotherapeutic platform. It is found that the X-ray-controlled ONOO--generation platform can efficiently improve the radiotherapy efficiency via directly damaging DNA, downregulating the expression of the DNA-repair enzyme, and overcoming the hypoxia-associated resistance in radiotherapy. Therefore, this SCNP-based platform may provide a new combinatorial strategy of ONOO- and radiotherapy to improve cancer treatment.