A Novel Near‐IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab Bioconjugates

• Published in: Chembiochem : a European journal of chemical biology Vol. 24; no. 15; pp. e202300203 - n/a
• Main Authors: Martínez‐Alonso, Marta, Gandioso, Albert, Thibaudeau, Chloé, Qin, Xue, Arnoux, Philippe, Demeubayeva, Nurikamal, Guérineau, Vincent, Frochot, Céline, Jung, Alain C., Gaiddon, Christian, Gasser, Gilles
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-08-2023; Wiley-VCH Verlag
• Subjects: Absorption; Acetonitrile; Antibodies; antibody; bioconjugation; cetuximab; Chemical Sciences; Irradiation; Light irradiation; Mass spectrometry; Mass spectroscopy; metals in medicine; Photodynamic therapy; Phototoxicity; Ruthenium; Ruthenium compounds; Singlet oxygen; metals in medicine; bioconjugation; ruthenium; cetuximab; antibody; photodynamic therapy
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202300203

A novel Ru(II) cyclometalated photosensitizer (PS), Ru‐NH2, for photodynamic therapy (PDT) of formula [Ru(appy)(bphen)2]PF6 (where appy=4‐amino‐2‐phenylpyridine and bphen=bathophenanthroline) and its cetuximab (CTX) bioconjugates, Ru‐Mal‐CTX and Ru‐BAA‐CTX (where Mal=maleimide and BAA=benzoylacrylic acid) were synthesised and characterised. The photophysical properties of Ru‐NH2 revealed absorption maxima around 580 nm with an absorption up to 725 nm. The generation of singlet oxygen (1O2) upon light irradiation was confirmed with a 1O2 quantum yield of 0.19 in acetonitrile. Preliminary in vitro experiments revealed the Ru‐NH2 was nontoxic in the dark in CT‐26 and SQ20B cell lines but showed outstanding phototoxicity when irradiated, reaching interesting phototoxicity indexes (PI) >370 at 670 nm, and >150 at 740 nm for CT‐26 cells and >50 with NIR light in SQ20B cells. The antibody CTX was successfully attached to the complexes in view of the selective delivery of the PS to cancer cells. Up to four ruthenium fragments were anchored to the antibody (Ab), as confirmed by MALDI‐TOF mass spectrometry. Nonetheless, the bioconjugates were not as photoactive as the Ru‐NH2 complex.
A new Ru(II) cyclometalated complex activatable at 740 nm is reported as a photosensitizer for photodynamic therapy. Two ruthenium‐cetuximab bioconjugates have been prepared to gain cancer cell specificity, but were found to be not phototoxic.