5-Aminolevulinic acid-induced oxidative stress on cells by gold nanoparticles.

金纳米颗粒对细胞产生 5-氨基乙酰丙酸诱导的氧化应激。

• 批准号: 7966145
• 负责人: PETER RIESZ
• 金额: $ 15.37万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7966145
• 关键词: Acids; Aminolevulinic Acid; Cancer cell line; Cell membrane; Cells; Chemotherapy-Oncologic Procedure; Citrates; Coupled; DNA; Drug Delivery Systems; Electron Spin Resonance Spectroscopy; Electrons; Esters; Generations; Gold; Heme; Human; Hydrogen Peroxide; Hydroxyl Radical; Incubated; Lipid Peroxidation; MCF7 cell; Mediating; Microsomes; Mitochondria; Monitor; Morphology; Organelles; Oxidative Stress; Oxides; Oxyhemoglobin; Particle Size; Photochemotherapy; Phototoxicity; Production; Reactive Oxygen Species; Sampling; Serum; Singlet Oxygen; Superoxide Dismutase; Superoxides; adduct; autooxidation; cancer cell; cancer therapy; catalase; cytotoxicity; fluidity; heme biosynthesis; insight; nanoparticle; protoporphyrin IX; pyrroline

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more of 5-ALA or 5-ALA-Me(for MCF-7) and 7 microg/ml of 15nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence and absence of AuNP's. Cytotoxicity was observed irrespective of the presence or absence of serum and medium. Production of reactive oxygen species ( ROS ) in cell-free samples was monitored by EPR (electron paramagnetic resonance ) as the DMPO-OH spin adduct (DMPO is 5,5-dimethyl-1-pyrroline N-oxide) and also showed a catalytic effect of gold nanoparticles. Both superoxide dismutase and catalase inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by the initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy.

5-mM浓度的氨基乙酰丙酸（5-ALA）及其甲酯（5-ALA-Me） 这些水平通过产生活性氧（ROS）诱导氧化应激。人类 癌细胞系（MCF-7和HepG 2）在黑暗中同时存在5.0 mM或更多的5-ALA或5-ALA-Me（对于MCF-7）和7 μ g/ml的15 nm柠檬酸盐封端金 纳米颗粒（AuNPs）的破坏更严重相比，在存在的 单独的乙酰丙酸。在电子显微镜照片中可以看到损伤， 在存在和不存在AuNP的情况下的形态。观察到细胞毒性， 血清和培养基的存在与否活性氧（ROS）的产生 通过EPR（电子顺磁共振）监测无细胞样品中的DMPO-OH 自旋加合物（DMPO是5，5-二甲基-1-吡咯啉N-氧化物），也显示出催化作用， 金纳米颗粒超氧化物歧化酶和过氧化氢酶均抑制活性氧的产生， 也降低了细胞样品中的细胞毒性。这些观察结果可以用 细胞外培养基中产生的ROS对细胞膜的初始攻击， 深入了解5-ALA在癌症化疗中的可能用途。