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.

Piano-stool Ru(II) complexes have emerged as a promising class of anticancer agents characterized by structural modularity and diverse cytotoxic activ…

Radiolabeled monoclonal antibodies (mAbs) form a major branch of nuclear medicine and are used in the development of tracers for both diagnostic imaging and molecularly targeted radio(immuno)therapy (RIT). Since treatment options for many types of late-stage cancers are limited and these diseases become refractory to classic chemotherapy, new tools are required to improve patient outcomes. The high tumor uptake and specificity of mAbs, coupled with increased therapeutic range of energetic β–-emitting radionuclides, offers a potential solution to overcome traditional problems associated with poor tissue penetration of antibody-drug conjugates, chemotherapeutic resistance, and off-target accumulation, which can lead to adverse responses. The challenge is to develop efficient and reliable chemical methods that provide simultaneous selectivity and high stabilization of the radiometal via complexation chemistry, with rapid access to new bioconjugate bonds on protein that avoid the loss of bioactivity. Here, we designed a new octadentate bispidine-chelating system, functionalized with a light-responsive tetrazole unit, and demonstrated the chemoselective derivatization of sulfhydryl groups introduced on the protein surface. High radiolabeling and bioconjugation yields of 161Tb-onartuzumab─an engineered mAb fragment targeting the human hepatocyte growth-factor receptor (c-MET; a characteristic biomarker found in clinical samples of several diseases, including gastric adenocarcinomas)─were obtained under ambient conditions after 5 min of light-induced coupling. Comprehensive biochemical and animal experiments including cellular binding assays, noninvasive γ-ray imaging, biodistribution studies, and pharmacokinetic measurements established the viability of using 161Tb-onartuzumab to target c-MET expression in vivo. Subsequent RIT studies in MKN-45 xenograft models demonstrated that the 161Tb-onartuzumab radiotracer formed by photoradiosynthesis permitted low-dose therapy studies that led to efficient targeting and treatment of tumor models. Collectively, the new complexation and chemoselective photoconjugation chemistries overcome some of the limitations in traditional labeling approaches. Photoradiosynthesis represents an excellent platform for building future antibody-based radiotracers for applications in diagnostic and therapeutic medicine.

Gold(III) organometallic complexes, particularly cyclometalated Au(III) compounds, have emerged as powerful tools in catalysis and bioinorganic chemistry, offering unique reactivity distinct from the...

Energy is essential for all life, and mammalian cells generate and store energy in the form of ATP by mitochondrial (oxidative phosphorylation) and non-mitochondrial (glycolysis) metabolism. These pro...

Metallacages (MCgs) are three-dimensional (3D)-supramolecular coordination complexes (SCCs) obtained by the self-assembly of metal ions with donor lig…

Iron is the most abundant transition metal element and would be the ideal replacement for noble metals in many applications that rely on luminescent and long-lived electronically excited states. We sh...