Irish Researchers Cite TLD1433 in new paperThey mention the current phase 2 bladder cancer trial and also the Roswell Park research demonstrating the destruction of lung cancer cells in vitro.
Phototoxicity of Tridentate Ru(II) Polypyridyl Complex with Expanded Bite Angles toward Mammalian Cells and Multicellular Tumor Spheroids Rhianne C. Curley, Christopher S. Burke, Karmel S. Gkika, Sara Noorani, Naomi Walsh, and Tia E. Keyes Publication Date: August 3, 2023 ..........................................................
Introduction
Photodynamic therapy (PDT) or photosensitized light therapy is a long standing medical treatment that has been applied to the treatment of cancers as well as infection and skin conditions. (1,2) The most common mode of application is that the photosensitizer (PS), under illumination by light of non-tissue destructive wavelengths, in the visible or near-infrared range (typically 630–800 nm), initiates the formation of singlet oxygen from ambient oxygen at the site of treatment to destroy the targeted cells. (3,4) In biological environments, singlet oxygen species typically have limited lifetimes (<3 μs), with an estimated half-life of approximately 40 ns and a diffusive distance of <268 nm. (5−7) Meaning the sensitizer must permeate the site of therapy. This format of PDT is known as type II PDT and constitutes the mechanism behind the majority of clinically approved PS for PDT, which have been based on tetrapyrrolic structures, for example, porphyrin, chlorin, and phthalocyanine. (8−11) Photofrin, for example, is a clinically approved PS hematoporphyrin derivative used for PDT treatment of, but not limited to, lung and esophageal cancer. (12) Many organic PS species traditionally applied to PDT have a number of drawbacks, including poor aqueous solubility, propensity for aggregation, skin photosensitivity, and dark toxicity. (13,14) There is, therefore, demand for the development of new classes of PS that address these issues. An ideal PS should be amphiphilic, display good solubility in biological media or water and exhibit minimum toxicity in the dark, but high toxicity when activated by a light source. Additionally, PS should be photostable given the short diffusive distances of singlet O2, they should be cell and tumor permeable. (15) Luminescent co-ordination compounds, such as those of ruthenium, are potentially very attractive agents for PDT as they are constitutionally triplet state emitters with high extinction coefficients (minimizing the PS dosage required) and have versatile chemistry that can be used to tune the properties of the compound to meet the demanding criteria of a PS. As they are usually charged, they tend not to self-aggregate into structures that diminish their photophysical properties or solubility and they have favorable photophysical properties, including good photostability. (16)
Metal polypyridyl luminophores are consequently under intensive investigation across a range of biological applications, including as luminescent probes for intracellular imaging, sensing, (17,18) as well as for their phototherapeutic potential in PDT. (19) Ru(II) complexes in particular are under study as sensitizers for routine type-II PDT applications, and type-II Ru(II) sensitizers have been rationally designed for 2-photon PDT. (20−23) TLD1433, a polypyridyl Ru(II) complex designed for the treatment of non-muscle-invasive bladder cancer (NMIBC), was the first Ru(II)-based PDT agent to enter a human clinical trial. (24) TLD1433 is administered through bladder instillation 1 h prior to light treatment and demonstrates high retention in bladder cancer cells. (25) Furthermore, Chamberlain et al. reported the successful destruction of A549 lung cancer cells in vitro upon irradiation of TLD1433 at 532 and 630 nm. (26).........................