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)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
United States
Zip Code
Bartelt, Alexander; Widenmaier, Scott B; Schlein, Christian et al. (2018) Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nat Med 24:292-303
Lim, Jong-Min; Cai, Truong; Mandaric, Stefan et al. (2018) Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective. J Colloid Interface Sci 538:45-50
Lo, Justin H; Hao, Liangliang; Muzumdar, Mandar D et al. (2018) iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer. Mol Cancer Ther 17:2377-2388
Chertok, Beata; Langer, Robert (2018) Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound. Theranostics 8:341-357
Mitchell, Michael J; Webster, Jamie; Chung, Amanda et al. (2017) Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis. Nat Commun 8:14179
Corbo, Claudia; Molinaro, Roberto; Tabatabaei, Mateen et al. (2017) Personalized protein corona on nanoparticles and its clinical implications. Biomater Sci 5:378-387
Shi, Jinjun; Kantoff, Philip W; Wooster, Richard et al. (2017) Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17:20-37
Arlauckas, Sean P; Garris, Christopher S; Kohler, Rainer H et al. (2017) In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med 9:
Bertrand, Nicolas; Grenier, Philippe; Mahmoudi, Morteza et al. (2017) Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nat Commun 8:777
Behzadi, Shahed; Serpooshan, Vahid; Tao, Wei et al. (2017) Cellular uptake of nanoparticles: journey inside the cell. Chem Soc Rev 46:4218-4244

Showing the most recent 10 out of 170 publications