Nanomaterial-based Approaches for Early Detection of Metastasis

基于纳米材料的转移早期检测方法

• 批准号: 8722466
• 负责人: ANGELA M. BELCHER
• 金额: $ 19.86万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8722466
• 关键词: Address; Adopted; Bacteriophages; Binding; Biological; Biological Markers; Blood; Blood Circulation; Blood Platelets; Cancer Biology; Cancer Center; Cell Survival; Cessation of life; Chemistry; Coupled; Detection; Development; Diagnostic; Diffusion; Disease; Distant; Drug Delivery Systems; Early Diagnosis; Engineering; Environment; Event; Exhibits; Growth; Half-Life; Host Defense; Image; Imaging Device; Investigation; Keratin; Keratin-19; Laboratories; Malignant Neoplasms; Membrane; Messenger RNA; Methods; Molecular; Multimodal Imaging; Nanotechnology; Neoplasm Circulating Cells; Neoplasm Metastasis; Organ; Pathway interactions; Patients; Peptide Fragments; Polymers; Preparation; Primary Neoplasm; Process; Property; Quantum Dots; Research; Research Personnel; Science; Semiconductors; Site; TACSTD2 gene; Technology; Therapeutic; Work; analog; base; cancer cell; cancer diagnosis; cancer therapy; design; fight against; fluorophore; in vivo imaging; interest; lymph nodes; nanocrystal; nanomaterials; nanoparticle; nanoscale; nanostructured; neoplastic cell; novel; outcome forecast; scaffold; sensor; small molecule; stoichiometry; tool; tumor; uptake; vector

Current work using nanotechnology-based approaches for cancer diagnosis and therapy has focused upon targeting and attacking the primary tumor. Less nanotechnology research has been geared toward metastasis. However, the dissemination of primary tumors to a secondary site is a multi-step process and is ripe for investigation using biological and engineering approaches to generate potential diagnostics and therapies. There are two events in the metastatic cascade that can be exploited towards design of diagnostics and therapeutics: (1) seeded secondary tumors and (2) cancer cells in circulation. Targeting tiny secondary tumors or dilute circulating tumor cells (CTCs) requires extremely high sensitivity and selectivity. We will adopt a two-pronged approach to address this problem, exploiting nanoarchitectures developed in our respective laboratories. Colloidal quantum dots (QDs, semiconductor nanocrystals) display a range of properties that make them attractive fluorophores for biological imaging applications with many advantages over their organic analogues. The Bawendi lab has pioneered the preparation and application of QDs for over 15 years, including some of the first QD sensors and in vivo imaging tools. Meanwhile, the Belcher group has established Ml 3 bacteriophage as a robust and versatile scaffold for templating the growth of a variety of inorganic nanomaterials. These nanoscale building blocks allow the genetically encoded construction of multifunctional agents displaying both nanoscale and molecular components. Each of these nanotechnologies has so-far demonstrated powerful capabilities, but they have yet to be applied to a target as challenging as cancer metastasis. Combining the chemistry and materials science expertise of our labs and the cancer biology expertise of our MIT/Harvard consortium, we will be able to create effective tools for the study, detection and treatment of metastases. We expect this work to be particularly complementary to Project 3, which concentrates on developing chip technologies for the detection of CTCs. Both projects will share some common challenges and we expect them to develop synergistically through regular contact between researchers within the consortium.

目前使用基于纳米技术的癌症诊断和治疗方法的工作重点是靶向和攻击原发性肿瘤。针对转移的纳米技术研究较少。然而，原发性肿瘤向继发部位的传播是一个多步骤的过程，并且使用生物和工程方法进行研究以产生潜在的诊断和治疗的时机已经成熟。转移级联中有两个事件可用于诊断和治疗的设计：（1）播种的继发性肿瘤和（2）循环中的癌细胞。针对微小的继发性肿瘤或稀释的循环肿瘤细胞 (CTC) 需要极高的灵敏度和选择性。 我们将采用双管齐下的方法来解决这个问题，利用我们各自实验室开发的纳米结构。胶体量子点（QD、半导体纳米晶体）具有一系列特性，使其成为生物成像应用中有吸引力的荧光团，与有机类似物相比具有许多优势。 Bawendi 实验室在量子点的制备和应用方面处于领先地位超过 15 年，其中包括一些首批量子点传感器和体内成像工具。与此同时，Belcher 小组已经建立了 Ml 3 噬菌体作为一种坚固且多功能的支架，用于模拟各种无机纳米材料的生长。这些纳米级构建块允许基因编码构建显示纳米级和分子成分的多功能制剂。迄今为止，这些纳米技术中的每一种都表现出了强大的能力，但它们尚未应用于像癌症转移这样具有挑战性的目标。结合我们实验室的化学和材料科学专业知识以及麻省理工学院/哈佛大学联盟的癌症生物学专业知识，我们将能够创建用于研究、检测和治疗转移的有效工具。我们希望这项工作能够与项目 3 形成特别的补充，项目 3 专注于开发用于 CTC 检测的芯片技术。这两个项目都将面临一些共同的挑战，我们希望它们能够通过联盟内研究人员之间的定期接触协同发展。