Nanoparticles As Promoters of Cell Longevity

描述(由申请人提供)： 工程学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结构方面。在这个建议中，PI(Rzigalinski)和co-PI(Seal)融合了细胞生物学和纳米材料科学的研究，以干预一个常见的生物医学病理，即自由基细胞损伤和衰老。我们通过一种新的无团聚改进的溶胶-凝胶工艺设计了2-20 nm的氧化铈纳米颗粒，并在使用大鼠脑细胞的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，氧化铈纳米颗粒可以延长培养脑细胞的寿命，延长2-3倍。在纳米颗粒处理的培养中，老化的神经元保持了功能性突触连接，并具有正常的细胞内钙信号。此外，氧化铈纳米颗粒还可以减少过氧化氢(H_2O_2)和紫外线诱导的细胞损伤超过65%。我们推测，氧化铈纳米颗粒独特的结构，就价结构和氧缺陷而言，可以通过清除自由基来延长细胞寿命，减少有毒物质的伤害。在这项建议中，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，并确定它们的作用机制。利用微阵列技术，对照细胞和纳米颗粒处理细胞的基因转录变化将在它们的生命周期内发生。最后，我们将检验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老年相关疾病的病理提供实质性的见解，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.