On the verge of exciting resultsMechanisms of action of Ru( ii ) polypyridyl complexes in living cells upon light irradiation The topic of this April 2019 scientific paper is the mechanism of action of ruthenium photosensitizers (such as TLD-1433), in living cells, when irradiated by light. It devotes several pages to the pre-clinical work done with TLD-1433 and its derivatives.
The authors, who are scientists unrelated to Theralase, working in France and Switzerland, are clearly talking about Theralase's clinical trial when they conclude that "very exciting results will be published in the near future."
Here is the conclusion of the paper:
"Conclusions and outlook
In recent years, many Ru(II) polypyridyl complexes were studied as potential PDT PSs. Their strong absorption in the visible light, ability to produce singlet oxygen upon light irradiation,
tunable photophysics and lack of cytotoxicity in the dark makes them very attractive candidates. Unfortunately, not many of them were analysed in-depth from a biological point of view. The mechanism of action of these compounds in living cells, a key factor in order to obtain their approval for a given indication, is very often still unknown or has only been superficially investigated. Worse, as shown in this Feature Article, there are only a few in vivo studies reported to date. However, despite this, one of such compounds has already entered clinical trial as a PDT PS against bladder cancer, clearly emphasising the potential of such complexes in this area of research. Further investigations in field of Ru(II) polypyridyl complexes as PDT PSs are of course needed. There is undoubtedly a necessity for new complexes that will exert their action by Type I mechanism. This is a crucial feature that will help fight very difficult to treat hypoxic tumours. During the designing process of the PDT PSs, adjustments will also need to be made in order to have PSs that can be activated at higher wavelengths. It is known that longer wavelengths will allow for deeper penetration through tissue. As shown in this Feature Article, this can also be obtained by Ru(II) polypyridyl complexes that are activated by two photon irradiation. However, this technique will require further proofs of its suitability for in vivo models, since studies in this field of research, not only with Ru(II) complexes, are for the moment much too scarce. Overall, we are convinced that this field of research is still in its infancy and that very exciting results will be published in the near future. "
It should be noted that Rutherrin, which will likely be the photosensitizer used in the coming phase 1 trials, also works in oxygen poor environments. and absorbs light throughougt the visible light spectrum and at NIR wavelengths (808 nm) "permitting the treatment of larger tissue volumes in vivo." (Neuro-Oncology Advances Article)