Development of Fluorescent and Magnetic Dual-Functional Probes for Molecular Imaging of Prostate Cancers
Zusammenfassung der Projektergebnisse
The aim of the project was to design and develop iron oxide nanoparticle-based dual modal contrast agents for magnetic resonance (MR) and optical imaging (OI) of prostate cancer. Iron oxide cores of size 5-6 nm with low polydispersity index were generated by co-precipitation under aqueous reaction conditions. Firstly, we tested lanthanide-doped iron oxide nanoparticles (Ln-USPIO). Unfortunately, these particles exhibited no florescence due to the low level of lanthanides incorporated into the iron crystal structure, which can be explained by the size-based difference between lanthanide and iron cations. Secondly, we attempted fluorescence coating of the nanoparticles using naphthalene disulfonic acids and its modified analogues, which also proved unsuccessful (although stable) due to quenching. Thereafter, we explored coating molecules, which are essentially non-quenching and relatively stable and endogenous as well. To this end, we used flavin analogues, which are endogenous and internalized by highly over-expressed riboflavin carrier proteins (RCP) in cancer and other metabolically active cells. Using flavin analogues, biocompatible, fluorescent and non-polymeric FMN- and FAD-decorated USPIO (FLUSPIO and FAD USPIO) were developed as versatile MR contrast agents. The superparamagnetic behavior of FLUSPIO/FAD USPIO was confirmed by MRI and SQUID. The biocompatibility of FLUSPIO and FAD USPIO was proven via different cell viability assays and stainings. FLUSPIO/FAD USPIO intensely and specifically accumulated in prostate cancer cells and activated endothelial cells (HUVEC) Also in vivo an intense accumulation of FAD USPIO was observed in prostate cancer xenografts when comparing to the clinically used SPIO agent Resovist. Thus, although being forced to change the initial study plan, we successfully developed a novel fluorescent USPIO for prostate cancer characterization and identified the RCP receptor as a promising target for molecular imaging.
Projektbezogene Publikationen (Auswahl)
- Opposing effects of RGD-labeled USPIO on glioma and endothelial cells” World Molecular Imaging Congress, 2008, Nice, France
Jochen Huppert, Chunfu Zhang, Jabadurai Jayapaul, Stefan Zwick, Eva C. Woenne, Margartea M. Mueller, Hanswalter Zentgraf, Michael Eisenhut, Yoseph Addadi, Michael Neeman, Wolfhard Semmler, Fabian Kiessling
- Dual modal contrast agent with novel non- polymeric fluorescent coating (FLUSPIO). World Molecular Imaging Congress, 2009, Montreal, Canada
Jabadurai Jayapaul, Michael Hodenius, Alexandra Buhl, Peter Comba, Fabian Kiessling, Jessica Gaetjens
- RGD-labeled USPIO inhibit adhesion and endocytotic activity of αvβ3 integrin expressing glioma cells and only accumulate in the vascular tumor compartment. Radiology 2009, 253(2):462-9
Kiessling F., Huppert J., Zhang C., Jayapaul J., Zwick S., Woenne E.C., Mueller M.M., Zentgraf H., Eisenhut M., Addadi Y., Neeman M., Semmler W.
- FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells. Biomaterials 2011, 32:5863-5871
Jayapaul J., Hodenius M., Arns S., Lederle W., Lammers T., Comba P., Kiessling F., Gaetjens J.
- Water-Soluble Superparamagnetic Magnetite Nanoparticles with Biocompatible Coating for Enhanced Magnetic Resonance Imaging (MRI). ACS Nano 2011, 5:6315- 6324
Xiao L., Li J., Brougham D.F.,Fox E.K., Feliu N., Bushmelev A., Schmidt A., Mertens N., Kiessling F., Fadeel B., Mathur S
- Fluorescent magnetoliposomes as a platform technology for functional and molecular MR and optical imaging. Contrast Media Mol Imaging 2012, 7:59-67
Hodenius M., Würth C., Jayapaul J., Wong J., Lammers T., Gätjensa J., Arns S., Mertensa N., Slabu I., Ivanova G., Bornemann J., De Cuyper M., Resch- Genger U., Kiessling F
(Siehe online unter https://doi.org/10.1002/cmmi.467)
