Novel nano-sized, biocompatible and stable free radical sensors for continuous in vivo hyperpolarization at ultra-low field MRI
The main goal of this project is preparation and detailed characterization of nano-sized and biocompatible free radicals that will be used as a contrast agent for continuous hyperpolarization of hydrogen nuclei at ultra-low field MRI. This research will be performed through four working packages (WPs) by a consortium consisting of four research groups with ample experience in diverse scientific disciplines. The initial step will be the preparation of small functionalized and long-lived free radicals or their precursors, which allow further synthetic modifications, i.e. coupling reactions with other functionalized molecules. The small-sized free radicals will be attached to different nano-sized biomolecular or biocompatible carriers such as the protein avidin, or dendrimers, polysiloxane-based nanoparticles and liposomes, respectively, which will further improve their biokinetic profiles and stability for in vivo utilization. Further modifications on the nano-sized carriers (incorporation of targeting vectors or other vehicle molecules) will be also performed in order to improve targeting properties of the resulting nano-sized free radicals and their accumulation in target tissue. Following the preparation of these bioconjugates, their thorough physicochemical and biophysical characterization will be performed, by investigating probe biocompatibility and potential toxicity towards the standard cell lines, as well as biokinetic profiles in biological tissues ex vivo. The ability of the final nano-sized probes to induce continuous hyperopolarization will be performed in buffered media (phantom experiments) at the in-house made SQUID-based ULF MRI system; finally, the preliminary imaging experiments on living animal subjects (rodents) will be performed to validate the overall approach.
Priv.-Doz. Dr. Goran Angelovski, MPI for Biological Cybernetics & University of Tuebingen
Igor A. Kirilyuk, PhD, Novosibirsk State University
Klaus Scheffler, MPI for Biological Cybernetics & University of Tuebingen
Prof. Pavle R. Andjus, Faculty of Biology University of Belgrade
Funding: 141.000 €