关键词: ceria nanoclusters mitochondria targeting oxidative stress radioprotective effect superoxide dismutase

Mesh : Cerium / chemistry pharmacology Animals Mitochondria / drug effects metabolism Reactive Oxygen Species / metabolism Mice Apoptosis / drug effects radiation effects Hematopoiesis / drug effects radiation effects Oxidative Stress / drug effects radiation effects Cell Survival / drug effects Radiation-Protective Agents / pharmacology chemistry Humans Radiation Protection / methods Cell Line

来  源:   DOI:10.2147/IJN.S459607   PDF(Pubmed)

Abstract:
UNASSIGNED: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.
UNASSIGNED: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).
UNASSIGNED: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.
UNASSIGNED: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.
摘要:
线粒体氧化应激是细胞凋亡的重要因素。氧化铈纳米材料具有清除自由基和模拟超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的巨大潜力。为解决氧化铈纳米材料靶向性差的问题,我们设计了白蛋白-氧化铈纳米簇(TPP-PCNLs),其目标是用磷酸三苯酯(TPP)修饰线粒体。TPP-PCNLs有望模拟超氧化物歧化酶的活性,不断去除活性氧,并在辐射防护中发挥持久作用。
首先,二氧化铈纳米团簇(CNLs),聚乙二醇二氧化铈纳米团簇(PCNLs),TPP-PCNLs的形态和大小进行了表征,紫外光谱,分散稳定性和细胞摄取,和共同定位随后,TPP-PCNLs的抗辐射作用进行了体外和体内实验,包括细胞活力,凋亡,彗星化验,组织病理学,和剂量减少因子(DRF)。
TPP-PCNLs表现出良好的稳定性和生物相容性。体外实验表明,TPP-PCNLs不仅可以很好地靶向线粒体,而且可以调节整个细胞中的活性氧(ROS)水平。更重要的是,TPP-PCNLs提高了L-02细胞线粒体的完整性和功能,从而间接消除线粒体氧化应激对细胞核DNA的持续损伤。TPP-PCNLs主要针对肝脏,脾,脾和其他髓外造血器官的辐射剂量降低因子为1.30。体内实验表明,TPP-PCNLs能有效提高小鼠的成活率,体重变化,受辐照动物的造血功能。Westernblot实验已证实TPP-PCNLs通过调节线粒体凋亡途径在辐射保护中发挥作用。
TPP-PCNLs通过靶向髓外造血器官-肝细胞和线粒体以持续清除ROS而发挥放射学保护作用。
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