A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer

Abstract

Copper is an earth-abundant and a biologically essential metal that offers a promising alternative to noble metals in photochemistry and photobiology. In this work, a series of sterically encumbered Cu(i) bis-phenanthroline complexes were investigated for their use in photochemotherapy (PCT). It was found that Cu(dsbtmp)2+ [dsbtmp = 2,9-disec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline] (compound 3), which possessed the longest excited state lifetime, exhibited significant in vitro photocytotoxicity on A375 (human malignant melanoma) and A549 (human lung carcinoma) cell lines. Fluorescence imaging demonstrated the significant uptake and localization of compound 3 in a perinuclear fashion. A comet assay indicated the induction of DNA damage in the dark. The DNA breaks were significantly amplified upon photoactivation. The light-induced enhancement of cytotoxicity was associated with the formation of reactive oxygen species (ROS), a known intermediate in photodynamic therapy (PDT). This successful demonstration of photocytotoxicity using long-lived cuprous phenanthroline paves the way to exploit this class of photosensitizers for PDT applications.

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

“…42 However cell viability results, under photoexcitation, were assessed against control cells exposed to light on the same plate. 13,20,23,26 In that perspective, the inuence of light, if any, was subtracted from the data allowing the assessment of the effect of drugs. While IC 50 values ranged between 5.55 mM (in MDA-BD-231 cells) and >100 mM (B16-F10 cells) in dark conditions, the values were as Fig.…”

“…log P values were measured for complexes 1 and 2 according to a modied procedure. 26 Briey, 0.5-2 mg of the chloride form of the complex were dissolved in 1 mL water saturated with octanol. 1 mL octanol saturated with water was then added and the mixture was shaken at 1400 rpm for 1 h at room temperature.…”

Improved Photostability of a CuI Complex by Macrocyclization of the Phenanthroline Ligands

“…Whereas the free ligands 6 , 7 , and 14 are white solids absorbing exclusively in the UV region, their Cu I complexes display characteristic metal‐to‐ligand charge‐transfer (MLCT) bands around 450 nm, which are displayed in Figure for the macrocyclic complex 1 and the open reference 15 recorded in CH 3 CN. Prominent absorption maxima are summarized in Table with comparison to [Cu(2,9‐Me 2 phen) 2 ][PF 6 ], which was synthesized according to literature . Oxygen atoms directly attached to the phenanthroline unit seem to diminish the intensity of the MLCT band .…”

“…Prominent absorption maxima are summarized in Table 1 with comparison to [Cu(2,9-Me 2 phen) 2 ][PF 6 ], which was synthesized according to literature. [37] Oxygen atoms directly attached to the phenanthroline unit seem to diminish the intensity of the MLCT band. [38,39] Furthermore, bulky substituents Solid-state structure of 11 with rotation ellipsoids at 50 % probability.…”

Recent Advances in Nanotheranostics for Treat‐to‐Target of Rheumatoid Arthritis

“…[56] PDT, a kind of developing phototherapy based on the property of photosensitizers generating ROS by light, has been explored for the last few decades. [136][137][138][139] Cerium oxide (CeO 2 ) NPs with unparalleled antioxidant properties are potential radical scavengers and redox cycling antioxidants because of the switch between Ce 3+ and Ce 4+ on the surface of NPs. [140,141] In addition, a study by Zhao et al explored the potential application of tetra sulfonatophenyl porphyrin (TSPP) in combination with TiO 2 nanowhiskers as an effective biomarker and PDT agent for RA theranostic.…”