Xavier University of Louisiana
Cancer-Specific Magnetic Imaging Agent
Quincy Brown, Tulane University
Galina Goloverda, Xavier University of Louisiana
Thomas Wiese, Xavier University of Louisiana
Pilot Project (May 1, 2021 - April 30, 2022)
Magnetic nanoparticles with tunable size for solving various biomedical diagnostics tasks are very attractive candidates for research and development, as they can be easily detected by MRI or MPI, and 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 selectively recognized by cancerous cells. These agents will be composed of individual 3-5 nm magnetic iron oxide particles coated with covalently bound organic oligomers, 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 amphiphilic spacer composed of 10-15 ethylene oxide units. These spacers will be conjugated at their termini with peptide-vectors responsible for the cell specificity (recognition). The idea is that these small particles will (a) avoid capturing by phagocytes, (b) exhibit fast pharmacokinetics, (c) penetrate through biological boundaries, (d) recognize the receptors at the surface of certain cancer cells, and (e) shorten the proton relaxation rates of the surrounding biological media and thus, act as MRI contrast agents. A fraction of the linker molecules will be conjugated with EPPT peptide, a known vector for targeting underglycosylated mucin-1 tumor antigen (uMUC1) overexpressed on the surface of cancer cells, or uMUC1 nucleotide aptamer. 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.