Over the past few decades, an abundance of information has been garnered regarding the biological profiles of cancer. It is now accepted that cancer is associated with a myriad of molecular and cellular processes. For example, the rapid proliferation of cancer cells has been linked to an increase in iron uptake and elevated levels of the transferrin receptor (TfR). This has led to the investigation of transferrin receptor as a target for both tumor detection and targeted therapeutics. The sensitivity of cancer detection and the efficacy of therapeutic treatment, however, can still be limited by an inadequate number of available TfR. In this proposal, we plan to examine whether pretreatment of murine tumor models with iron chelators can lead to a further increase in expression of the TfR. In particular, we will examine whether the additional TfR sites made available following iron depletion will allow for a significant increase in the binding of TfR-targeted superparamagentic iron oxide nanoparticles and improved MR contrast at the tumor site.
The specific aims of this approach are (1) to compare and contrast different targeting agents for labeling the TfR with magnetic nanoparticles and (2) evaluate the ability of DFO to improve TfR-targeting in vivo. The long-term goal is to develop a versatile and efficient approach for cancer detection and treatment in the clinic.
We propose to explore whether pretreatment of living subjects with iron chelators can lead to improved accumulation of transferrin receptor-targeted agents at tumor sites. This approach could allow for more sensitive and earlier detection of tumors and also increase the efficacy of targeted therapeutics.
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| Cheng, Zhiliang; Thorek, Daniel L J; Tsourkas, Andrew (2010) Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent. Angew Chem Int Ed Engl 49:346-50 |
| Elias, Drew R; Cheng, Zhiliang; Tsourkas, Andrew (2010) An intein-mediated site-specific click conjugation strategy for improved tumor targeting of nanoparticle systems. Small 6:2460-8 |
