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


Karges, Johannes; Heinemann, Franz; Jakubaszek, Marta; Maschietto, Federica; Subecz, Chloé; Dotou, Mazzarine; Vinck, Robin; Blacque, Olivier; Tharaud, Mickaël; Goud, Bruno; Viñuelas Zahı́nos, Emilio; Spingler, Bernhard; Ciofini, Ilaria; Gasser, Gilles (2020). Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy. Journal of the American Chemical Society, 142(14):6578-6587.

Abstract

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 sometimes limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted toward 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 tissues and, therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of a DFT guided search for efficient PDT PSs with a substantial spectral red shift toward the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex that 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.

Abstract

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 sometimes limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted toward 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 tissues and, therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of a DFT guided search for efficient PDT PSs with a substantial spectral red shift toward the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex that 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Life Sciences > Biochemistry
Physical Sciences > Colloid and Surface Chemistry
Uncontrolled Keywords:Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis
Language:English
Date:8 April 2020
Deposited On:17 Apr 2020 11:12
Last Modified:13 May 2020 23:44
Publisher:American Chemical Society (ACS)
ISSN:0002-7863
OA Status:Closed
Publisher DOI:https://doi.org/10.1021/jacs.9b13620
Project Information:
  • : FunderH2020
  • : Grant ID648558
  • : Project TitleSTRIGES - Escaping from the Franck-Condon region : a theoretical approach to describe molecular STructural ReorganIzation for reversible EnerGy and information storage at the Excited State
  • : FunderH2020
  • : Grant ID681679
  • : Project TitleTowards Novel Inert (Photo-)toxic Ru(II) Polypyridyl Complexes
  • : FunderANR
  • : Grant IDANR-10-IDEX-0001-02 PSL
  • : Project Title

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Embargo till: 2021-03-14