The objective of this research is to develop ultra-sensitive magnetic resonance imaging (MRI) probes based on MFe2O4 (M=Fe, Co, Mn)-loaded polymer micelles for cancer molecular imaging applications. MRI is a powerful clinical imaging modality that has wide applications in the non-invasive diagnosis and post-therapy assessment for cancer and other diseases. Currently, low sensitivity of detection (approximately 10[-4] M) of conventional MR contrast agents severely limits their applications in monitoring molecular processes in vivo. In this application, we will investigate MFe2O4 (M=Fe, Co, Mn)-loaded polymer micelles as a new multifunctional platform of MRI probes with high sensitivity and biological specificity. Recently, monodisperse MFe2O4 nanocrystals have been successfully developed with fine tuning of particle size below 20 nm. These nanocrystaline materials have demonstrated unique super-paramagnetic (e.g. CoFe2O4) or ferromagnetic (e.g. CoFe2O4) properties. Herein we propose to develop a novel nanocomposite construct consisting of inorganic MFe2O4 nanoparticles loaded inside the hydrophobic cores of amphiphilic polymer micelles. We hypothesize that MFe2O4 -loaded polymer micelles will provide a safe and ultra-sensitive MRI probe for molecular imaging applications. In one specific application, we will functionalize micelle surface with a cyclic Arg-Gly-Asp (cRGD) peptide and examine the imaging of alpha(v)beta(3) receptors on the angiogenic endothelial cells in the tumor neo-vasculature.
The specific aims are: (1) Investigate the MR relaxivity and sensitivity of MFe2O4 -loaded polymer micelles;(2) Evaluate the safety and biocompatibility of the MFe2O4 -loaded polymer micelles;and (3) Evaluate the effectiveness of cRGD-functionalized, MFe2O4 -loaded polymer micelles in imaging alpha(v)beta(3) receptors in rabbit VX-2 tumors. This R21 funding will provide critical support to establish MFe2O4 -loaded polymer micelles as a safe and sensitive MR imaging probe for in vivo molecular imaging. If successfully established, these MR probes will provide a powerful technology platform that can exploit the plethora of molecular targets identified in cancer biology for early cancer detection and/or non-invasive assessment of post-therapy outcome.
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