Nanomaterial-based Approaches for Early Detection of Metastasis

目前使用基于纳米技术的方法进行癌症诊断和治疗的工作集中在靶向和攻击原发性肿瘤上。较少的纳米技术研究已经面向转移。然而，原发性肿瘤向继发部位的传播是一个多步骤的过程，并且对于使用生物学和工程学方法进行研究以产生潜在的诊断和治疗已经成熟。在转移级联中有两个事件可以用于诊断和治疗的设计：（1）接种的继发性肿瘤和（2）循环中的癌细胞。靶向微小的继发性肿瘤或稀释的循环肿瘤细胞（CTC）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架构。胶体量子点（QD，半导体纳米晶体）显示出一系列的性质，使它们成为生物成像应用中有吸引力的荧光团，与它们的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开创了超过15年的历史，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M13噬菌体作为用于模板化各种无机纳米材料的生长的稳健且通用的支架。这些纳米级构件允许遗传编码的多功能试剂的构建，其显示纳米级和分子组分。到目前为止，这些纳米技术中的每一种都表现出了强大的能力，但它们还没有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。我们希望这项工作能够特别补充项目3，该项目专注于开发用于检测CTC的芯片技术。这两个项目将面临一些共同的挑战，我们希望它们通过联盟内研究人员之间的定期接触协同发展。

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.