Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

Johannes Karges, Shi Kuang, Federica Maschietto, Olivier Blacque, Ilaria Ciofini, Hui Chao () and Gilles Gasser ()
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Johannes Karges: PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology
Shi Kuang: Sun Yat-sen University
Federica Maschietto: PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Theoretical Chemistry and Modelling
Olivier Blacque: University of Zurich
Ilaria Ciofini: PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Theoretical Chemistry and Modelling
Hui Chao: Sun Yat-sen University
Gilles Gasser: PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E′)-4,4′-bisstyryl-2,2′-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.

Date: 2020
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DOI: 10.1038/s41467-020-16993-0

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