Multifunctional and multiplexed nanoparticles for molecular imaging and treatment of breast cancer.

Abstract

Abstract Abstract #6003 Multifunctional nanoparticles with the ability to target tumors, provide molecular imaging and to deliver therapeutic agents hold great promise for improving the survival of cancer patients. We have developed multifunctional nanoparticles targeted to cellular receptors that are highly expressed in breast cancer and tumor stromal cells. Fluorescent quantum dot (QD) or magnetic iron oxide (IO) nanoparticles are conjugated to either the amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA) or to a single chain antibody against the epidermal growth factor receptor (ScFvEGFR), resulting in uPAR or EGFR targeted nanoparticles. Since the binding of ATF peptides or ScFvEGFR to their receptors results in blocking receptor function and internalization of the receptor-ligand complex, these targeted imaging probes can also inhibit tumor growth and deliver drugs. Using near infrared fluorescence (NIR) dye-labeled targeting peptides, we demonstrate specificity of these targeting ligands in an orthotopic human breast cancer model in nude mice. We found that tail vein injection of a mixture of Cy5.5 dye-ATF and IRDye 800-ScFvEGFR peptides leads to the selective accumulation of both probes in human breast cancer xenografts and NIR optical imaging of the tumors in the mammary fat pad of nude mice (Fig. A).
 
 We show that uPAR- and EGFR-targeted nanoprobes display different patterns of intratumoral distribution with EGFR probes in the central area and uPAR probes in the peripheral and central regions of the tumor, which may be the results of expressing uPAR in the invasive edge of tumor cells and tumor stromal cells and EGFR only in tumor cells. In vivo optical imaging using ATF-nanoparticles is also demonstrated in human breast cancer xenograft (Fig. B) and in mouse mammary tumor lung metastatic models. Furthermore, magnetic Cy5.5-ATF IO nanoparticles are multimodality imaging probes for both optical and MR tumor imaging. Since magnetic IO nanoparticles are biodegradable and relatively safe for human use, we have developed a therapeutic imaging nanoparticle by encapsulating doxorubicin into the polymer coating of the nanoparticles and have shown selective delivery of the drug and cytotoxic effect in breast cancer cells in vitro. Results of our study show that multifunctional and multiplexed nanoparticles have great potential for the development of novel tumor imaging and therapeutic approaches. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6003.