The reliance of many anticancer agents on apoptosis often limits their therapeutic efficacy and contributes to the development of drug resistance. To overcome these challenges, alternative mechanisms ...

Ferroptosis, a recently described form of regulated, nonapoptotic cell death mechanism, presents significant potential for cancer treatment, particularly when combined with photodynamic therapy (PDT)....

Photodynamic therapy (PDT) harnesses the combination of light, oxygen, and photosensitizers to induce cell death via reactive oxygen species (ROS) formation. Given its intrinsic properties, PDT repres...

The blood-brain barrier represents a significant challenge in delivering anticancer drugs for glioblastoma treatment. The study investigates the potential of a series of octahedral photoactivatable cyclometalated iridium complexes (Ir1–Ir10) with the general formula [Ir(ttpy)(C∧N)Cl]PF6 as photoactivated therapy candidates for the treatment of this aggressive tumor. These complexes, which include the terdentate ligand 4′-(p-tolyl)-2,2′:6′,2″-terpyridine (ttpy), and a C∧N ligand based on the deprotonated 2-arylbenzimidazole backbone, were tested on human glioblastoma using 2D cell cultures and 3D spheroidal models, including a fusion system comprising cerebral organoids from nonmalignant human-induced pluripotent stem cells and spheroids derived from malignant brain cells. The iridium complexes catalyze NADH photooxidation and photogenerate 1O2 and/or •OH under blue light irradiation. Blood-brain barrier penetration was assessed using various in vitro models. The complex Ir4, containing deprotonated methyl 1-butyl-2-phenylbenzimidazolecarboxylate, shows promise for targeted therapy of resistant brain tumors when photoactivated with blue light. Ir4 induces rapid and sustained ROS-mediated cytotoxicity and selectively accumulates in tumor tissue. This suggests its potential for fluorescently guided-PDT cooperative resection of glioblastoma. Notably, Ir4 significantly reduces glioblastoma growth even under dark conditions compared to conventional Temozolomide treatment without affecting healthy brain tissue.

Luminescence and photochemistry involve electronically excited states that are inherently unstable and therefore spontaneously decay to electronic ground states, in most cases by nonradiative energy release that generates heat. This energy dissipation can occur on a time scale of 100 fs (∼10–13 s) and usually needs to be slowed down to at least the nanosecond (∼10–9 s) time scale for luminescence and intermolecular photochemistry to occur. This is a challenging task with many different factors to consider. An alternative emerging strategy is to target dissociative excited states that lead to metal–ligand bond homolysis on the subnanosecond time scale to access synthetically useful radicals. Based on a thorough review at the most recent advances in the field, this article aims to provide a concise guide to obtaining luminescent and photochemically useful coordination compounds with d-block elements. We hope to encourage “photo-motivated” chemists who have been reluctant to apply their synthetic and other knowledge to photophysics and photochemistry, and we intend to stimulate new approaches to the synthetic control of excited state behavior.