X‐Ray‐Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4:Ce3+ Scintillators and their Applications for Radiosensitization,Advanced Materials

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X‐Ray‐Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4:Ce3+ Scintillators and their Applications for Radiosensitization
Advanced Materials ( IF 27.4 ) Pub Date : 2018-09-10 , DOI: 10.1002/adma.201804046
Zhen Du _{1,

2} , Xiao Zhang _{1,

2} , Zhao Guo _{1,

2} , Jiani Xie _{1,

2} , Xinghua Dong _{1,

2} , Shuang Zhu ₁ , Jiangfeng Du ₃ , Zhanjun Gu _{1,

2} , Yuliang Zhao _{1,

2,

4}

Affiliation

Peroxynitrite (ONOO⁻), the reaction product derived from nitric oxide (NO) and superoxide (O₂^−•), 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 O₂^−• simultaneously when excited by X‐ray irradiation. Such simultaneous release of NO and O₂^−• 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.

中文翻译：

基于纳米LiLuF4：Ce3 +闪烁体的X射线控制过氧亚硝酸盐生成及其在放射增敏中的应用

过氧亚硝酸盐（ONOO ^-），从一氧化氮产生的反应产物（NO）和超氧化物（O ₂^{- •}），是一种有效的氧化剂和硝化剂调制复杂生物过程和促进细胞死亡。因此，可以预期，ONOO的生产过剩^-在肿瘤可以是在癌症治疗中的有效方法。这里，多官能透视控制ONOO ^-报道了基于闪烁纳米粒子（SCNP）和紫外线响应NO供体的新一代平台，鲁辛的黑盐，因此阐明了其在增强放射治疗疗效中的应用机理。归因于SCNPs的放射致发光和高X射线吸收特性，当通过X射线辐射激发时，纳米复合材料可同时产生NO和O _2-^•。NO的这种同时发布和O ₂^{- •}确保了高效的透视控制代ONOO的^-在肿瘤。同时，在此纳米治疗平台中，使用X射线作为激发源可以达到更好的穿透深度并诱导放射治疗。据发现，X射线控制ONOO ^-新一代平台可通过直接破坏DNA，下调DNA修复酶的表达并克服放射治疗中与低氧相关的耐药性，有效地提高放射治疗效率。因此，这种基于SCNP平台可以提供ONOO的新组合的策略^-和放射治疗，以改善癌症治疗。

更新日期：2018-09-10

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