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NANO2021-Nanoteknologi og nye materiale

Synchrotron-Assisted Design of Cancer Phototherapeutics

Alternativ tittel: Synkrotron-assistert design av kreft-fototerapeutika

Tildelt: kr 12,0 mill.

Synkrotroner er store sirkelformede maskiner som akselerer ladde partikler i en lukket sløyfe. De ladde partiklene avgir stråling som kan brukes til å bestemme strukturen til et molekyl som igjen gir muligheten til å finjustere egenskapene til molekylet. Vi vil bruke denne metoden til å optimalisere molekyler for bruk i fototerapi av kreft. Molekylene som skal brukes er inspirert av hemoglobin og klorofyll, som er ringformede molekyler med et jern- eller magnesiumatom i sentrum. I vårt tilfelle vil jern- eller magnesiumatomet bli byttet ut med et tungmetall som gull eller platina. Ved å gjøre det endrer vi egenskapene til disse molekylene slik at vi kan bruke dem til andre formål, og da spesielt for å oppdage og behandle kreft

The continuing need for early diagnosis and improved therapeutics for cancer will drive a program of basic research in medicinal inorganic chemistry, with emphasis on fundamental 5d and 4f element coordination chemistry, closely coupled with biological testing of new compounds at collaborating laboratories. The project targets a new class of compounds, the 5d element complexes of porphyrin analogues (to date substantially limited to corroles and our own laboratory), as a source of new compounds for cancer imaging and therapy. Unusual metal-ligand interactions, probed with synchrotron-based X-ray spectroscopies (including conventional and HERFD XAS/XANES, XES, and RIXS), will advance fundamental knowledge of heavy element bonding. Many of the complexes are expected to exhibit room temperature phosphorescence; photophysical measurements and state-of-the-art quantum chemistry calculations will be used to derive design principles for new phosphorescent substances. In a second work package, the same will be attempted for lanthanides, based on a set of capped porphyrin analogue ligands that will be specially synthesized for this project. The third and final work package will focus on solubilization and bio/nano/radio-conjugation strategies for porphyrin analogues. Thus, we will use and develop green approaches toward cross-coupling reactions to derive new water-soluble porphyrin analogue ligands and complexes. Conjugation studies will center around remolding the aforementioned phosphorescent complexes as tumor-targeting imaging agents, as photosensitizers in photodynamic and photothermal therapy, and as combined therapeutic and diagnostic reagents (theranostics).

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NANO2021-Nanoteknologi og nye materiale