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

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 (O-1(2)) upon light irradiation was confirmed with a O-1(2) 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.

Automated summary

A novel Ru(II) cyclometalated photosensitizer, Ru-NH2, and its bioconjugates, Ru-Mal-CTX and Ru-BAA-CTX, were synthesized and characterized. Ru-NH2 showed absorption maxima around 580 nm and generated singlet oxygen upon light irradiation. In vitro experiments demonstrated the excellent phototoxicity of Ru-NH2 towards CT-26 and SQ20B cells under specific light conditions.