X-Ray-Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4 :Ce3+ Scintillators and their Applications for Radiosensitization.
Zhen DuXiao ZhangZhao GuoJiani XieXinghua DongShuang ZhuJiangfeng DuZhanjun GuYuliang ZhaoPublished in: Advanced materials (Deerfield Beach, Fla.) (2018)
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.
Keyphrases
- high resolution
- early stage
- dual energy
- cancer therapy
- locally advanced
- dna repair
- radiation induced
- radiation therapy
- nitric oxide
- cell death
- high throughput
- electron microscopy
- drug delivery
- computed tomography
- dna damage
- poor prognosis
- rectal cancer
- squamous cell carcinoma
- hydrogen peroxide
- oxidative stress
- cell proliferation
- energy transfer
- dna damage response
- magnetic resonance
- optical coherence tomography
- liquid chromatography
- aqueous solution
- tandem mass spectrometry
- simultaneous determination