Theralase Technologies Inc. V.TLT

Two-photon of ROS storm in ruthenium(II) Feb 2024

[Oden6570]

Over the last years, much interest has been devoted to photodynamic therapy (PDT). During this treatment, the patient is locally or systemically injected with a photosensitizer and then exposed to irradiation. Upon light exposure, the photosensitizer is excited to a long-lived triplet state that can generate reactive oxygen species (ROS) by energy transfer or electron transfer reactions. These species are highly reactive and generate oxidative stress inside the cancer cells, leading to cell death [11], [12]. Among the most promising photosensitizers (PSs), Ru(II) polypyridine complexes have emerged due to their attractive photophysical and biological properties [13], [14]. Notably, the compound TLD-1433 is currently studied in phase II clinical trials in Canada for non-muscle-invasive bladder cancer. Despite these promising properties, the majority of Ru(II) polypyridine complexes are excited with ultraviolet or blue light [15], [16], [17]. As these wavelengths are poorly penetrating the tissue, these PSs could only find use for superficial applications. To enable the treatment of deep-seated or large tumors, PSs with an excitation within the biological spectral window (600–900 nm) are needed. Recent studies have shown that this could be achieved by compounds that could absorb two photons of low energy simultaneously, also referred to as two-photon PDT. Despite promising preliminary results, the reported Ru(II) polypyridine complexes in the literature have generally a poor two-photon absorption, limiting the application of this technique [18], [19], [20], [21], [22]. To overcome this drawback, there is a need for the development of new compounds or materials with significantly higher twoTwo-photon phototriggering of ROS storm in ruthenium(II) coordinated carbon nitride for robust cancer immunotherapy - ScienceDirect-photon absorption.