Nanotechnology enabled targeting of p53 deficiency in human cancer

项目摘要/摘要 癌症是一个主要的全球健康问题，也是美国第二大死亡原因。这个 癌症的早期发现对于阻止癌症的扩散至关重要。循环中的肿瘤细胞(CTC)是一个标志 癌症的这种侵袭性行为。这些细胞从原发肿瘤中分离出来，破坏基底 血管的膜，并迁移到血液或淋巴循环中。他们转移到遥远的地方 它们在组织中适应新的微环境，最终播种和定居形成转移。 目前的癌症检测技术不够灵敏，无法在癌症的最早阶段发现癌症。 然而，现有的治疗方法只有在癌症尚未转移的情况下才能有效。因此，存在 能够在转移之前及早发现癌症，可以提高存活率。 最近的研究发现，CTCs携带有关原发肿瘤的信息，并有可能成为 对癌症诊断和进展有价值的生物标志物。它们还允许分子表征某些特定的 原发肿瘤的生物学特性。CTCs的分子表征已被证明具有很大的 有可能评估癌症的表型和基因特征，而不需要侵入性活检 原发肿瘤。这使得能够对癌症进行微创患者监测和反应评估 治疗。然而，血液中CTC的低浓度和现代技术阻碍了CTC的检测 对于CTC的检测有几个主要缺点，如重复性低，敏感性和特异性低。 这个补充应用程序的目标是创建一种从血液中捕获CTCs的有效方法 癌症患者样本具有较高的重复性、敏感性和特异性，可用于癌症早期检测。这将是 通过制造镀金的电-微流控器件，在 主通道(AuZones芯片)，并使用图案化的介电泳力将细胞从流动区引导到 捕捉区。捕获区和流动区的这种分离将大流量的负面影响降至最低 速度。聚二甲基硅氧烷(PDMS)电微流控装置将被覆盖一层15 nm厚的金层 用硫代化捕获抗体进行表面修饰。硫代捕获抗体将通过 镀金电微流控装置，用捕获的抗体修饰主通道表面 通过利用金和硫醇基团之间的高亲和力。患者血液中CTCs表面抗原的检测 将允许它们被修改在设备表面的抗体捕获，因为高抗原性- 抗体结合亲和力。这一补充剂申请的另一个重要目标是促进健康的多样性- 相关研究。这将通过培训少数群体的博士后来实现，他们将成为 鼓励更多少数群体参与生物医学科学研究。

Project Summary/Abstract Cancer is a major global health problem and is the second leading cause of death in the United States. The early detection of cancer is vital to help stop the spread of cancer. Circulating tumor cells (CTCs) are a hallmark of this invasive behavior of cancer. These cells detach from the primary tumor, break down the basement membrane of blood vessels, and migrate into the blood or lymphatic circulation. They translocate to distant tissues where they adapt to the new microenvironment, and eventually seed and colonize to form metastases. Current cancer detection techniques are not sensitive enough to be able to detect cancer at its earliest stage. However, existing treatments could be effective only when cancer has not metastasized yet. Therefore, being able to detect cancer early before metastasis increases survival rates. Recent studies have found that CTCs carry information about the primary tumor and have the potential to be valuable biomarkers for cancer diagnosis and progression. They also allow molecular characterization of certain biological properties of the primary tumor. Molecular characterization of CTCs has proven to have a great potential to assess the phenotypic and genotypic features of a cancer without the need for invasive biopsy of the primary tumor. This allows for minimally invasive patient monitoring and response assessment of cancer treatment. However, CTC detection is hindered by its low concentration in blood and contemporary techniques for CTC detection have had several major drawbacks such as low repeatability, sensitivity, and specificity. The goal of this supplemental application is to create an effective approach to capture CTCs from blood samples of cancer patients with high repeatability, sensitivity, and specificity for early cancer detection. This will be achieved by fabricating a gold-coated electro-micro-fluidic device with distinct capture and flow zones in the main channel (AuZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed. The polydimethylsiloxane (PDMS) electro-micro-fluidic device will be coated with a 15 nm thick gold layer and surface modified with thiolated capturing antibody. Thiolated capturing antibodies will be flown through the gold-coated electro-micro-fluidic device, to modify the surface of the main channel with the capturing antibody by utilizing the high affinity between gold and the thiol group. The surface antigens on CTCs from patient blood will allow them to be captured by antibodies modified on the surface of the device due to the high antigen- antibody binding affinity. Another important goal of this supplement application is to promote diversity in health- related research. This will be achieved by training postdoc from a minority group, who will be exemplary to encourage more minority groups to participate in biomedical science research.