Nanoparticles As Promoters of Cell Longevity

纳米颗粒作为细胞寿命的促进剂

基本信息

批准号：
7102696
负责人：
BEVERLY A RZIGALINSKI
金额：
$ 36.86万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2008-07-31
项目状态：
已结题

项目摘要

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重大进步，尤其是材料科学和纳米级设备的分子结构。在此提案中，PI（Rzigalinski）和Co-Pi（密封）已将细胞生物学和纳米级材料科学的研究合并，以干预常见的生物医学病理学，即自由基细胞损伤和衰老。我们已经通过一种新型的非凝聚修饰的溶胶 - 凝胶过程设计了2-20 nm的氧化元素纳米颗粒，并使用大鼠脑细胞评估了这些颗粒在组织培养模型中的活性。我们的初步数据表明，氧化葡萄纳米颗粒在培养中延长了2-3倍的培养物。纳米颗粒处理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，氧化岩纳米颗粒减少了过氧化氢（H2O2）和紫外线诱导的细胞损伤超过65％。我们假设，关于价结构和氧缺损，氧化岩纳米颗粒的独特结构可通过清除自由基来促进细胞寿命并减少毒性损伤。在此提案中，我们将合成并进一步表征氧化葡萄纳米颗粒的物理和化学特性，并确定其在生理相关的液体和细胞内环境中的行为。我们将进一步剖析纳米颗粒在细胞寿命中的作用，并确定其作用机理。使用微阵列技术，对照和纳米颗粒处理的细胞中基因转录的改变将在其寿命中。最后，我们将研究氧化葡萄纳米颗粒增加果蝇中寿命的能力。这些研究将为衰老和与年龄相关的疾病的病理提供大量见解，并启动纳米技术方法的药物治疗。