The goal of the proposed study is to develop therapeutic imaging nanoparticles for targeted drug delivery and non-invasive tumor imaging of primary and metastatic breast cancer. We hypothesize that systemic delivery of peptide-conjugated iron oxide nanoparticles targeting to urokinase plasminogen activator receptor (uPAR) leads to selective accumulation and internalization of the iron oxide nanoparticles in breast cancer cells. This allows delivery of therapeutic agents that are encapsulated in the iron oxide nanoparticles into the tumor cells. Enrichment of the iron oxide nanoparticles in tumor cells and tumor environment generates strong magnetic signals for detection of primary and metastatic breast cancer lesions as well as real-time monitoring of therapeutic effects by magnetic resonance imaging. The proposed research will be the first to use multifunctional nanoparticles that selectively target to breast cancer cells and tumor environment, and have the ability to deliver therapeutic agents into the cells. It is well known that high levels of uPAR are present in all stages of breast cancer and are closely associated with aggressive tumor types and poor prognosis. Therefore, the proposed nanoparticles are therapeutic imaging nanoparticles that have great potential for future clinical application in detection and treatment of breast cancer.
