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Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

preprint
submitted on 10.12.2019 and posted on 17.12.2019 by Johannes Karges, Franz Heinemann, Marta Jakubaszek, Federica Maschietto, Chloé Subecz, Mazzarine Dotou, Olivier Blacque, Mickaël Tharaud, Bruno Goud, Emilio Vinuelas Zahinos, Bernhard Spingler, Ilaria Ciofini, Gilles Gasser
The utilization of Photodynamic Therapy (PDT) for the treatment of various types of cancer has gained increasing attention over the last decades. Despite the clinical success of approved photosensitizers (PSs), their application is limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted towards the development of metal complexes and especially Ru(II) polypyridine complexes based on their attractive photophysical and biological properties. Despite the recent research developments, the vast majority of complexes utilize blue or UV-A light to obtain a PDT effect, limiting the penetration depth inside the tissue and therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of the DFT guided search for efficient PDT PSs with a substantial spectral red shift towards the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex, which causes phototoxicity in the very-low micromolar-to-nanomolar range at clinically relevant 595 nm, in monolayer cells as well as in 3D multicellular tumor spheroids.

History

Email Address of Submitting Author

gilles.gasser@chimieparistech.psl.eu

Institution

Chimie ParisTech, PSl University, CNRS

Country

France

ORCID For Submitting Author

0000-0002-4244-5097

Declaration of Conflict of Interest

Not available

Exports