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

Johannes Karges (1) , Shi Kuang , Federica Maschietto (1) , Olivier Blacque (2) , Ilaria Ciofini (3) , Hui Chao , Gilles Gasser (1)

1 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 LECIME - Laboratoire d'Electrochimie, Chimie des Interfaces et Modélisation pour l'Energie (LECIME - UMR 7575)

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.

Mots clés: Cancer - Thérapeutique; Bioinorganic chemistry

Domaines: Chimie thérapeutique

Johannes Karges, Shi Kuang, Federica Maschietto, Olivier Blacque, Ilaria Ciofini, et al.. Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-16993-0⟩. ⟨hal-02890539⟩