Nanomaterial-based Approaches for Early Detection of Metastasis

目前使用纳米技术进行癌症诊断和治疗的工作主要集中在靶向和攻击原发肿瘤上。针对肿瘤转移的纳米技术研究较少。然而，原发性肿瘤向继发部位的扩散是一个多步骤的过程，利用生物学和工程方法进行研究以产生潜在的诊断和治疗方法的时机已经成熟。在转移级联中有两个事件可以用于诊断和治疗的设计：(1)种子继发性肿瘤和(2)循环中的癌细胞。靶向微小继发性肿瘤或稀释循环肿瘤细胞（ctc）需要极高的灵敏度和选择性。

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.