Exploitation of Long-Lived ³IL Excited States for Metal–Organic Photodynamic Therapy: Verification in a Metastatic Melanoma Model

Abstract

Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized, characterized according to their photophysical and photobiological properties, and evaluated for their collective potential as photosensitizers for metal-organic photodynamic therapy. The dyads in this series possess lowest-lying (3)IL-based excited states with lifetimes that can be tuned from 22 to 270 μs in fluid solution and from 44 to 3440 μs in glass at 77 K. To our knowledge, these excited-state lifetimes are the longest reported for Ru(II)-based dyads containing only one organic chromophore and lacking terminal diimine groups. These excited states proved to be extremely sensitive to trace amounts of oxygen, owing to their long lifetimes and very low radiative rates. Herein, we demonstrate that (3)IL states of this nature are potent photodynamic agents, exhibiting the largest photocytotoxicity indices reported to date with nanomolar light cytotoxicities at very short drug-to-light intervals. Importantly, these new agents are robust enough to maintain submicromolar PDT in pigmented metastatic melanoma cells, where the presence of melanin in combination with low oxygen tension is known to compromise PDT. This activity underscores the potential of metal-organic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.

Synthesis, Characterization, and Biological Evaluation of New Ru(II) Polypyridyl Photosensitizers for Photodynamic Therapy

“…72 Luminescence lifetimes in the μs-range implicate a long-lived triplet excited state, which is thought to be important for efficient photosensitization. 37 Altogether, complex 1 showed luminescence lifetimes favorable for photosensitization. The luminescence emission spectrum of 2 shows only weak intensity (Fig S1), which is reflected by a low emission quantum yield of <0.1%.…”

Lightening up Ruthenium Complexes to Fight Cancer?

“…This activation can be acceptable for particular kinds of superficial cancer such as melanoma. [59,60] On the other hand, in order for metal-based PSs candidates to compete with the currently approved PSs, it is definitively necessary to develop compounds which are activatable at higher wavelengths. Another important point which will need to be addressed in the future is the translation of the interesting results obtained on a cellular level into in vivo studies.…”

Photo-induced cytotoxicity and anti-metastatic activity of ruthenium(ii)–polypyridyl complexes functionalized with tyrosine or tryptophan

“…Synthesis of Complexes 1 and 2: Complexes 1 and 2 were synthesized following previously reported literature procedures. The chloride salts of 1 and 2 were obtained by anion metathesis of their respective PF 6ˉ salts using [nBu 4 …”

“…For absorption titrations, complexes 1 and 2 were converted to their chloride salts by treatment with [nBu 4 N]Cl in acetone. Complex solution (10 mL of a 10 mmol stock) in Tris-HCl buffer was then diluted into Tris buffer to give a final concentration of about 5 mm Tris buffer.…”

“…Photodynamic therapy (PDT) is non-invasive and one of the most extensively used techniques for dermatological diseases and various types of cancers, which could be used to control and selectively treat solid tumors. [2][3][4] The main advantage of PDT over traditional therapies such as surgery, radiation and chemotherapy are that PDT produces fewer side effects. PDT requires a photosensitizer or photosensitizing agent (PS) that is therapeutically activated in the presence of light.…”