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.

Public Health Relevance

Metastasis is a process in which tumor cells separate from a primary tumor, penetrate the bloodstream and lymph nodes, evade host defenses, exit circulation and colonize distant organs. This final step in tumor development is responsible for more than 90% of cancer related deaths. A method for detecting and halting metastasis would be a watershed event in the fight against cancer. Detection of metastasis would allow for earlier and more effective disease prognosis and would provide a clearer picture of a tumor's malignancy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Massachusetts Institute of Technology
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