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NANO2021-Nanoteknologi og nye materiale

Synchrotron-Assisted Design of Cancer Phototherapeutics

Alternative title: Synkrotron-assistert design av kreft-fototerapeutika

Awarded: NOK 12.0 mill.

Synchrotrons are large circular machines that accelerate charged particles around a closed-loop path. The charged particles emit electromagnetic radiation, including X-rays, which can be used for a variety of scientific studies. Among other things, synchrotron radiation may be used to determine a compound's structure and thereby to design new compounds with desired properties. We will use this method to optimize cancer phototherapeutics. The actual substances to be used are inspired by the natural compounds hemoglobin and chlorophyll, which are ring-shaped molecules containing an iron or a magnesium at the center. In our case, the iron or magnesium will be exchanged by a heavy metal such as gold or platinum. Doing so will repurpose these naturally inspired molecules for our own goals, in particular cancer imaging and therapy.

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).

Funding scheme:

NANO2021-Nanoteknologi og nye materiale