Nanomaterial-based Approaches for Early Detection of Metastasis

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肿瘤。针对转移的纳米技术研究较少。然而，原发肿瘤扩散到继发部位是一个多步骤的过程，使用生物学和工程方法进行研究的时机已经成熟，以产生潜在的诊断和治疗方法。在转移级联中有两个事件可用于诊断和治疗设计：(1)种子继发性肿瘤和(2)循环中的癌细胞。靶向微小的继发性肿瘤或稀释性循环肿瘤细胞(CTCs)需要极高的灵敏度和选择性。 我们将采取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体系结构。胶体量子点(量子点，半导体纳米晶)表现出一系列的性质，使它们具有许多优于有机类似物的优点，在生物成像应用中具有吸引力。15年来，巴文迪实验室一直是量子点制备和应用的先驱，包括一些最早的量子点传感器和体内成像工具。与此同时，Belcher团队已经建立了ml3噬菌体作为一种强大和多功能的支架，用于模板各种无机纳米材料的生长。这些纳米级的构建块允许以基因编码的方式构建同时显示纳米级和分子组件的多功能试剂。到目前为止，这些纳米技术中的每一项都显示出了强大的能力，但它们还没有被应用到像癌症转移这样具有挑战性的目标上。结合我们实验室的化学和材料科学专业知识以及我们麻省理工学院/哈佛大学联盟的癌症生物学专业知识，我们将能够为转移的研究、检测和治疗创造有效的工具。我们预计这项工作将特别补充项目3，该项目专注于开发用于检测四氯化碳的芯片技术。这两个项目将面临一些共同的挑战，我们预计它们将通过联盟内研究人员之间的定期接触而协同发展。

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.