discovered_01_2015

discovered 01 .15 PORTRAIT WWW.HZDR.DE chemistry and standing on her own feet. ‘After finishing my PhD I really wanted to broaden my scientific horizons,’ says Kubeil. Equipped with little more than a suitcase, she is now heading Down Under to investigate a young research field that is at least as unexplored as the Australian Outback. ‘The first complexes for the targeted release of carbon monoxide were only developed around the turn of this century,’ the chemist explains. CO, which can be used to treat issues like inflammatory diseases and high blood pressure, cannot be directly injected into the bloodstream. It can even be lethal if the doses are high enough because it bonds irreversibly with the red blood pigment hemoglobin. ‘Then you suffocate,’ says Kubeil. That is why CO releasing molecules, or CORMs, were developed, a class of metal carbonyl complexes. ‘You can change the pH value, add enzymes or expose the carbonyl complexes to light so that they release CO in the right place at the right time.’ Releasing gas with light Kubeil’s task is to develop carbonyl complexes that release CO when they are exposed to light. But light in the visible spectral range barely penetrates the tissue – a disadvantage when trying to reach deep-seated tumors. Kubeil consequently uses infrared light that can penetrate further into the tissue, combined with so-called up-converting nanoparticles. Upon irradiation of these special nanoparticles with infrared light they convert it into visible light. This activates the carbonyl complexes that Kubeil attaches all over the surface of the up-converting nanoparticles and releases the carbon monoxide. The latter, in its turn, exerts the desired effect on the tumor. To accumulate the nanoparticles in the tumor, Kubeil will also equip them with target-seeking molecules. They attach themselves to structures in the cell membrane that occur particularly in cancer cells. First square meters, then nanometers A tight schedule Manja Kubeil intends to get through with the help of her experienced mentors – the 2014 Helmholtz Award winner Leone Spiccia from the School of Chemistry at Monash University, who will be a visiting researcher in Dresden in 2015, and Bim Graham from Monash Institute of Pharmaceutical Sciences. ‘They have a lot of experience with metal carbonyl complexes there, but there isn’t one that can absorb light in the visible range,’ Kubeil comments. When the chemical part of the undertaking is finished she wants to see how the ‘flatulent nanoparticles’ behave in the cells. Using spectroscopic methods and even the synchrotron on the edge of Melbourne the German chemist intends to trace the miniscule particles – less than one ten-millionth of a millimeter – in the cell. What happens to the decomposition products of the metal complexes after CO has been released? Are they eliminated from the cell or do they damage the cell? Do the nanoparticles wander into the cell or stay outside? There are many questions still to be answered. But the first important one on Manja Kubeil’s list has nothing to do with nanometers, but rather, square meters: whether she will be able to find a convenient apartment for herself and her husband in chronically crowded Melbourne. PUBLICATIONS: K. Zarschler, M. Kubeil, H. Stephan: Establishment of two complementary in vitro assays for radiocopper complexes achieving reliable and comparable evaluation of in vivo stabili- ty, in RSC Advances 2014 (DOI: 10.1039/c3ra47302c) J. A. Barreto, W. O’Malley, M. Kubeil, B. Graham, H. Stephan, L. Spiccia: Nanomaterials: Applications in cancer imaging and therapy, in Advanced Materials 2011 (DOI: 10.1002/ adma.201100140) _Institute of Radiopharmaceutical Cancer Research at HZDR Dr. Manja Kubeil manja.kubeil@monash.edu CONTACT SEPARATION: Laboratory bottles with various solvents for a special HPLC procedure to separate and analyze the substances. Photo: Frank Bierstedt

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