Magnetic Nanoparticle Probe This project focuses on development of magnetic iron oxide nanoparticles (MIONs) for eventual use in molecular imaging using magnetic resonance. Our goals have been to develop a small (< 20 nm) iron oxide nanoparticle that is biocompatible and functionalized. Currently available iron oxide-based contrast agents are larger (20-40 nm), with a heterogeneous coating of dextran. We have coated MIONs with a micelle-based approach, using phospholipids modified with a polyethylene glycol (PEG) polymer. The size of these particles (dependent upon the length of the PEG polymer) is on the order of 15 nm. The PEG portion of the phospholipids allows us to vary functional groups that are available for conjugation of a variety of ligands, ranging from targeting molecules to delivery peptides to fluorescent dyes. Shown below in figure A is a cartoon depicting a MION (gray) coated with a phospholipid-PEG monolayer to which has been attached the fluorescent dye, Texas Red, and the delivery peptide, Tat. Figure B shows these particles upon delivery into living cells, and Figure C shows negative contrast that is detectable in cells with MIONs (spot 3) as compared to cells without MIONs (spot 2). We are currently working on variations of the micelle coating to optimize contrast and determine basic mechanisms of contrast. We are also working towards characterizing the behavior of this contrast agent in vivo.