Nanoparticles As Promoters of Cell Longevity

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展，特别是在材料科学和纳米器件的分子结构方面。在这项提案中，PI（Rzigalinski）和co-PI（Seal）合并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。我们已经设计了氧化铈纳米粒子，2-20 nm，通过一种新的非团聚改性溶胶-凝胶过程，并评估这些粒子在组织培养模型中使用大鼠脑细胞的活性。我们的初步数据表明，氧化铈纳米颗粒延长了培养中脑细胞的寿命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，并且具有正常的细胞内钙信号传导。此外，氧化铈纳米颗粒将过氧化氢（H2 O2）和UV光诱导的细胞损伤减少超过65%。我们推测，氧化铈纳米颗粒的独特结构，相对于价态结构和氧缺陷，促进细胞寿命，并通过清除自由基减少毒性损伤。在这项提案中，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颗粒在细胞寿命中的作用，并确定其作用机制。使用微阵列技术，对照和纳米颗粒处理的细胞中基因转录的改变将在其寿命期间发生。最后，我们将研究氧化铈纳米颗粒增加果蝇寿命的能力。这些研究将为衰老和年龄相关疾病的病理学提供实质性的见解，并启动药物治疗的纳米技术方法。

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.