Nanoprobes and integrated nanodevices for cancer detection and treatment

描述(申请人提供)：恶性黑色素瘤是世界上增长最快的癌症。目前检测转移性黑色素瘤的方法是不够的。至少有20%的患者会患上晚期疾病，这种疾病很少治愈。在这项申请中，我们提出了一项针对纳米技术专家的电气工程师的培训计划，以便他能够更好地了解癌症，特别是黑色素瘤的早期发现的临床需求。这种培训经验将使申请者成为一名精通癌症生物学和纳米技术的真正跨学科专家。它还将在申请者和赞助商之间建立持久的合作，探索癌症纳米技术的新领域。培训将分为两个阶段：(1)了解和识别黑色素瘤的DNA和RNA生物标记物；(2)开发用于检测和操作生物标记物的纳米技术平台。需要研究的生物标记物包括BRAF突变、黑素皮质素1受体突变和microRNA表达。我们将研究其在黑色素瘤细胞和正常黑素细胞中的表达水平及其影响。将特别强调了解它们与将同时开发的纳米探测器一起产生的影响。纳米级的探针将被优化，以在极低的浓度下快速、高特异性地检测黑色素瘤细胞。具体地说，我们将研究新的纳米探针的合成和连接技术，其中将包括贵金属纳米粒子、纳米棒和纳米壳。使用这些探针，我们将研究两个技术平台：(1)基于流体的技术，其中纳米探针被悬浮并在溶液中与其他生物分子(例如血液样本)相互作用；(2)通过纳米探针注入黑色素瘤细胞进行光学成像和靶向。对于(1)，我们将开发一种高度集成的纳米和微流控系统，在该系统中，可以精确地操纵和检测微观数量的样品，以进行高灵敏度的检测和成像。对于(2)，我们将详细研究不同细胞对纳米探针的摄取过程，以及纳米探针在细胞内的动力学和相互作用。 与公众健康相关：恶性黑色素瘤是世界上增长最快的癌症，至少20%的黑色素瘤患者发展为晚期疾病，这种疾病很少治愈。因此，早期发现的方法是高度优先的，迫切需要有效治疗和管理这种疾病的新战略。拟议的培训计划寻求将纳米技术应用于黑色素瘤细胞的检测和治疗。

DESCRIPTION (provided by applicant): Malignant melanoma is the most rapidly increasing cancer throughout the world. Current methods for detection of metastatic melanoma are not adequate. At least 20% of patients develop advanced disease, which is rarely curable. In this application, we propose a training program for an electrical engineer who is an expert in nanotechnology so that he can better understand the clinical needs for early detection of cancer, especially melanoma. This training experience will establish the applicant as a truly interdisciplinary expert well versed in both cancer biology and nanotechnology. It will also establish a lasting collaboration between the applicant and the sponsors that will explore the new frontiers of cancer nanotechnology. The training will have two phases: (1) understanding and identifying DNA and RNA biomarkers for melanoma and (2) developing nanotechnology platform for detection and manipulation of the biomarkers. The biomarkers to be investigated include BRAF mutations, melanocortin 1 receptor mutations, and microRNA expression. We will study the expression levels and their effects in melanoma cells and normal melanocytes. A particular emphasis will be placed on understanding their effects in conjunction with the nanoprobes to be developed concurrently. The nanoscale probes will be optimized for rapid, high-specificity detection of melanoma cells at extremely low concentrations. Specifically, we will investigate new synthesis and conjugation techniques for nanoprobes which will include noble metal nanoparticles, nanorods and nanoshells. Using these probes, we will investigate two technology platforms: (1) fluidic-based technique in which nanoprobes are suspended and interact with other biomolecules in solution (e.g., blood sample); and (2) optical imaging and targeting by nanoprobe injection into melanoma cells. For (1), we will develop a highly integrated nano- and micro-fluidic system in which a microscopic amount of sample is accurately manipulated and examined for high-sensitivity detection and imaging. For (2), we will investigate in detail the intake process of nanoprobes by various cells and the dynamics and interaction of nanoprobes inside the cell. RELEVANCE TO PUBLIC HEALTH: Malignant melanoma is the most rapidly increasing cancer throughout the world and at least 20% of melanoma patients develop advanced disease which is rarely curable. Methods for early detection is therefore a high priority and new strategies for effective treatment and management of the disease are highly desired. The proposed training program seeks to apply nanotechnology to the detection and treatment of melanoma cells.