Multimeric and Nanoscale Bioresponsive Probes for Functional MRI

• Applicant: Privatdozent Dr. Goran Angelovski
• Subject Area: Pharmacy ; Biological and Biomimetic Chemistry
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 365513518

Nano-sized materials play an essential role in modern nanomedicine, particularly for various imaging purposes, drug delivery, therapy or a combination of these applications. In molecular imaging, contrast agents based on nanocarriers are greatly appreciated for their advantageous pharmacological properties and possibility to carry various functional molecules, thus allowing multimodal readout, targeted accumulation or signal amplification. Magnetic resonance imaging (MRI) can greatly benefit from using these functional and multimeric contrast agents. For instance, they could be employed in neuroimaging to monitor neural activity directly, and improve the current state-of-the-art methodology that is yet not ideal and based on the indirect signal resulted from hemodynamics and neurovascular coupling. To this aim, we propose preparation of nano-sized bioresponsive contrast agents, sensitive to aspects of neurophysiological changes. As such, these nanoprobes would be able to produce signals that are directly linked to neuronal processing, providing a robust magnetic response to concentration changes of extracellular calcium ions and specific neurotransmitter (NT) molecules, which can be translated to a contrast change in MRI. More specifically, we plan to couple our monomeric and potent bioresponsive contrast agents that show very favorable properties to liposome or cyclodextrin carriers. Besides possessing sensor properties, these agents will be equipped with targeting ligands which increase the probe tissue retention time and improve its pharmacokinetic properties. Following the preparation, the detailed structural and physicochemical characterization of these macromolecules will be performed. Ultimately, the MRI in vivo experiments in living rodents will be done to validate the activity of these probes.The novel nano-sized contrast agents are anticipated to result in considerably larger MR responses, better specificity towards the target ion or molecule, improved biocompatibility and delivery into the target tissue. They will bring a new momentum in the chemistry of contrast agents and encourage further development of other bioresponsive probes. Moreover, monitoring calcium/NT levels and fluctuations will allow direct correlation of signal changes with neuronal activity by means of novel fMRI technique. These new insights will be extremely valuable for neuroimaging in studying brain function, may aid early detection of neurodegenerative diseases and be a great asset to molecular imaging in general.

• DFG Programme: Research Grants