Spanish researchers cite the pioneering phase 2 trial of
TLD1433 PDT as the cause of renewed interest in oncological photodynamic therapy.
Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes JBIC Journal of Biological Inorganic Chemistry (2023
Published: 15 April 2023
Piedad Herrera-Ramrez, Sarah Alina Berger, Dana Josa, David Aguil, Ana B. Caballero, Pere Fontova, Vanessa Soto-Cerrato, Manuel Martnez & Patrick Gamez
"Introduction
The impact of cancer on society is major as it currently represents the second leading cause of death worldwide [1]. Chemotherapy is one of the most common types of cancer treatment [2]. Nevertheless, it often suffers from some severe and unpleasant side effects [3], as observed with the well-known chemotherapeutic drug cisplatin [4], whose efficacy can even be reduced leading to platinum-resistant tumours [5]. The development of more selective and efficient anticancer agents to overcome adverse effects and drug resistance is therefore a topical field of research [6, 7]. Various approaches may be applied to improve the selectivity and efficiency of chemical drugs, such as the use of targeting groups [8], nanoparticles [9], stimuli-responsive drug-delivery systems [10] or stimuli-activatable prodrugs (e.g., activation through pH, light, sound, redox environment, etc.) [11,12,13,14]. Due to the possibility to switch them on in a controllable manner, photoactivatable compounds are currently experiencing a great deal of attention from the scientific community, mostly for antibacterial [15], dermatologic [16] or anticancer [11] applications. The increasing interest in the possible use of photoresponsive, metal-based anticancer drugs stems from the highly promising properties of TLD-1433, a polypyridyl Ru(II) complex reported by McFarland, Lilge and co-workers [1], which has entered Phase II clinical trials for the treatment of non-muscle invasive bladder cancer (NMIBC) [2]. Hence, numerous transition-metal-containing photosensitizers have been described in the literature for potential utilization in photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) [17,18,19].
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Polypyridyl ruthenium(II) compounds represent a highly promising family of photoactive complexes; they are stable under both dark and light conditions, exhibit strong light absorption and efficiently mediate the generation of singlet dioxygen [1, 31]. For instance, the ruthenium(II) complex TLD-1433 has a remarkably high quantum yield of 1O2 production and is therefore highly photocytotoxic toward cancer cells [32, 33]."