Cancer diagnostics remains one of major challenges of biomedical science. One of the most promising approaches relies on using an imaging agent which can recognize and bind to the cancerous cells, and then be detected by optical or MRI imaging. Ultrasmall magnetic nanoparticles with a tunable size are very attractive candidates for such an imaging agent development because they can be easily detected by MRI or MPI, and also because they can be constructed using stable and relatively non-toxic materials, such as iron oxides and/or ferrites. In this project we will develop new imaging agents which can be selectively recognized by cancerous cells. These agents will be composed of our "home-made" individual 3-5 nm magnetic iron oxide particles coated with covalently bound organic oligomers of an optimal size, so that overall size of the nanoparticulate adduct will not exceed 15-20 nm. The organic coating for these particles (linker molecules) is our own recently developed composition consisting of 2-hydroxyisophtalate (tenacate) coordinating head and an amphiphilic spacer composed of a variable-length ethylene oxide units. These spacers will be conjugated at their termini with biomolecules responsible for the cell specificity (vectors). It is known that an underglycosylated mucin-1 antigen (uMUC-1) is overexpressed in most of human malignant cells. This antigen can be specifically recognized by some peptides and oligonucleotides, which can be used as vectors attached to the imaging agent. The idea is that relatively small magnetic particles containing such a vector can be engineered to provide the optimal properties to (a) be "stealthy" and avoid capturing by phagocytes, (b) exhibit tunable pharmacokinetics, (c) exhibit tunable penetration through the biological boundaries, (d) recognize the receptors at the surface of the certain cancer cells, and (e) shorten the proton relaxation rates of the surrounding biological media and thus, act as effective MRI contrast agents. In our imaging agent, the length and structure of the linker molecules will be adjusted for optimal pharmacokinetic properties. A fraction of them will be conjugated with EPPT peptide or a custom-made nucleotide aptamer, both known as vectors for targeting mucin-1 tumor antigen. We will perform in vitro studies in uMUC1-positive and negative cell lines to assess specificity, cellular uptake, cellular distribution and toxicity of the nanoparticles, as a function of the organic shell structure and size. Pharmacokinetics will be studied in the next phase of the project. Our hypothesis is that targeted superparamagnetic nanoparticles of an average size of 15-20 nm will have a high level of specific binding to uMUC-1 antigen on the surface of cancer cells, but a reduced level of nonspecific binding to blood serum proteins. Therefore they will have a chance to avoid phagocytic clearance as well as early renal clearance and become an effective tool for early detection of cancer. Involvement of undergraduate students is part of the educational component of this project. Students will be trained in organic and inorganic synthesis and a variety of characterization methods, which will prepare them for their future careers in graduate or professional schools.