Nanoparticles As Promoters of Cell Longevity

纳米粒子作为细胞寿命的促进剂

• 批准号: 6782517
• 负责人: BEVERLY A RZIGALINSKI
• 金额: $ 37.52万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6782517
• 关键词: Drosophilidae; X ray crystallography; aging; bioengineering /biomedical engineering; calcium ion; cell age; cerium; cytotoxicity; fluorescence spectrometry; free radical scavengers; genetic transcription; hydrogen peroxide; laboratory rat; microarray technology; microglia; nanotechnology; particle; photoelectron spectrometry; tissue /cell culture; transmission electron microscopy

DESCRIPTION (provided by applicant): The field of engineering has made substantial advances in nanotechnology, particularly in materials science and the molecular construction of nanoscale devices. In this proposal, the PI (Rzigalinski) and co-PI (Seal) have merged the studies of cell biology and nanoscale materials science to intervene in a common biomedical pathology, that being free radical cell damage and aging. We have engineered cerium oxide nanoparticles, 2-20 nm, by a novel non-agglomeration modified sol-gel process and assessed the activity of these particles in a tissue culture model using rat brain cells. Our preliminary data suggests that cerium oxide nanoparticles prolong brain cell longevity in culture, by 2-3 fold. Aged neurons in nanoparticle treated cultures maintained functional synaptic connections and had normal intracellular calcium signaling. Further, cerium oxide nanoparticles reduced hydrogen peroxide (H2O2) and UV light - induced cell injury by over 65%. We hypothesize that the unique structure of cerium oxide nanoparticles, with respect to valence structure and oxygen defects, promotes cell longevity and decreases toxic insults by scavenging free radicals. In this proposal we will synthesize and further characterize the physical and chemical properties of cerium oxide nanoparticles, and determine their behavior in physiologically relevant fluids and in the intracellular environment. We will further dissect the role of nanoparticles in cell longevity and determine their mechanism of action. Using microarray technology, alterations in gene transcription in control and nanoparticle treated cells will be during their lifespan. Lastly we will examine the ability of cerium oxide nanoparticles to increase longevity in the fruit fly. These studies will provide substantial insight into the pathology of aging and age-associated disorders and initiate a nanotechnological approach to pharmacotherapy.

描述（由申请人提供）： 工程领域在纳米技术方面取得了实质性进展，特别是在材料科学和纳米器件的分子构造方面。在该提案中，PI (Rzigalinski) 和 co-PI (Seal) 融合了细胞生物学和纳米材料科学的研究，以干预常见的生物医学病理学，即自由基细胞损伤和衰老。我们通过一种新颖的非团聚改性溶胶-凝胶工艺设计了 2-20 nm 的氧化铈纳米颗粒，并使用大鼠脑细胞在组织培养模型中评估了这些颗粒的活性。我们的初步数据表明，氧化铈纳米颗粒可将培养物中的脑细胞寿命延长 2-3 倍。纳米颗粒处理的培养物中的老化神经元保持功能性突触连接并具有正常的细胞内钙信号传导。此外，氧化铈纳米颗粒可将过氧化氢 (H2O2) 和紫外线引起的细胞损伤减少 65% 以上。我们假设氧化铈纳米粒子的独特结构（在价态结构和氧缺陷方面）可通过清除自由基来促进细胞寿命并减少毒性损伤。在本提案中，我们将合成并进一步表征氧化铈纳米颗粒的物理和化学性质，并确定它们在生理相关液体和细胞内环境中的行为。我们将进一步剖析纳米粒子在细胞寿命中的作用并确定其作用机制。使用微阵列技术，对照细胞和纳米颗粒处理的细胞中基因转录的改变将在其生命周期内发生。最后，我们将研究氧化铈纳米颗粒延长果蝇寿命的能力。这些研究将为衰老和与年龄相关的疾病的病理学提供深入的见解，并启动药物治疗的纳米技术方法。