Li Hong, Yang Zhang-You, Liu Cong, Zeng Yi-Ping, Hao Yu-Hui, Gu Ying, Wang Wei-Dong, Li Rong
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China.
Free Radic Biol Med. 2015 Oct;87:26-35. doi: 10.1016/j.freeradbiomed.2015.06.010. Epub 2015 Jun 24.
Ceria nanoparticles (CNPs) have recently been shown to protect cells and animals from radiation-induced damage. However, most of the CNPs used in previous studies were either naked or weakly protected by surfactants, which inevitably encounter many obstacles in biological applications. Here, alendronate was used as an ideal anchor to graft polyethylene glycol (PEG) onto CNPs, leading to enhanced stability, reduced cytotoxicity, and improved biological properties. Further investigation assessed the protective ability of the nanoparticles against radiation-induced effects for human normal liver cells (L-02), indicating that the PEGylated CNPs (CNPs-AL-PEG) were more efficient than naked CNPs. We determined that enhanced Ce(3+)/Ce(4+) ratios improved intracellular dispersion and that the ameliorated intracellular distribution of CNPs-AL-PEG contributes to the elevated expression of SOD2, which leads to increased protection of normal cells against ROS and reduces the oxidatively generated DNA damage. These studies hold tremendous promise for radioprotection and biological applications.
二氧化铈纳米颗粒(CNPs)最近已被证明能保护细胞和动物免受辐射诱导的损伤。然而,先前研究中使用的大多数CNPs要么是裸纳米颗粒,要么仅被表面活性剂微弱地保护,这在生物应用中不可避免地会遇到许多障碍。在此,阿仑膦酸盐被用作理想的锚定物,将聚乙二醇(PEG)接枝到CNPs上,从而提高了稳定性,降低了细胞毒性,并改善了生物学特性。进一步的研究评估了纳米颗粒对人正常肝细胞(L-02)辐射诱导效应的保护能力,表明聚乙二醇化的CNPs(CNPs-AL-PEG)比裸CNPs更有效。我们确定,增强的Ce(3+)/Ce(4+)比率改善了细胞内的分散性,并且CNPs-AL-PEG改善的细胞内分布有助于超氧化物歧化酶2(SOD2)表达的升高,这导致对正常细胞免受活性氧(ROS)的保护增加,并减少氧化产生的DNA损伤。这些研究在辐射防护和生物应用方面具有巨大的前景。