Reactive oxygen species (ROS) are highly reactive molecules derived from molecular oxygen that play critical roles in cellular signaling, homeostasis, and the regulation of various physiological and pathological processes. Accurate detection and quantification of ROS are essential for elucidating their roles in health and disease. Despite significant advances in ROS probe development, challenges persist due to their short lifetimes, high reactivity, and their chemical diversity. This perspective article provides a critical evaluation of the limitations of the most commonly applied probe molecule DCFH-DA. Capitalizing on this, recommendations with practical applications in the lab for the specific detection of hydrogen peroxide, hydroxyl radical, singlet oxygen, superoxide anion, and peroxynitrite are provided. By integrating current knowledge on ROS probe technologies, this work aims to guide researchers in reliably assessing ROS in complex biological systems, thereby facilitating a deeper understanding of ROS-mediated processes and their implications for disease research and therapeutic development.

Photodynamic therapy (PDT) is a promising strategy for head and neck squamous cell carcinoma (HNSCC), but the immune consequences of tumor cell death remain incompletely understood. We compared two ruthenium(II) polypyridine photosensitizers (PSs) in HNSCC models and found that both were potently phototoxic (nanomolar IC50s), triggered diverse cell death pathways (including autophagy and ferroptosis), and promoted hallmark danger signals of immunogenic cell death (ICD). Strikingly, only one PS induced apoptosis and strong endoplasmic reticulum (ER) stress, yet paradoxically led to immune tolerance in vivo. Conversely, the PS that did not induce apoptotic cell death with milder stress responses resulted in a better antitumor immunity in vivo. These unexpected findings challenge the prevailing view that PDT-triggered apoptosis and ER stress are essential for ICD. Our study underscores the complexity of PDT-induced cell death balance and immunogenic signals and highlights the need to redefine ICD-inducing criteria for the rational design of next-generation PSs.

The coordination capacity of thiosemicarbazone ligands and their synergism with palladium(II) ions modulate their reactivity, allowing custom design. Using thiosemicarbazones with two potential stable...

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.

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...

Despite the potential of photodynamic therapy (PDT), this oxygen-dependent oncological treatment is greatly restricted in the clinic by the well-known hypoxic feature of solid tumors. Here we provide ...

Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance to conventional therapies, leading to poor patient outcomes. This challenges the effi...

Rhobo6 is a cell-impermeable small-molecule fluorophore that displays reversible fluorogenic binding to glycans, making it a general, wash-free, and non-perturbative label for the extracellular matrix...

The relaxation pathway and excited state dynamics of [Ru(N3)(N2)(PTA)]2+ type Ru(II)-polypyridyls containing phosphorus-based monodentate ligand PTA (1,3,5-triaza-7-phosphaadamantane) from the photog...

Glioblastoma multiforme (GBM) is highly aggressive, necessitating new therapies. Photoactivated chemotherapy (PACT) offers a promising approach by activating prodrugs with visible light at the tumor site. This study evaluated the anticancer activity of ruthenium-based PACT compounds in U-87MG glioblastoma cells and their safety in SH-SY5Y neuron-like cells. The compound [3](PF6)2 showed promising light-activated anticancer effects in U-87MG cells, while [1](PF6)2 was inactive, and [2](PF6)2 was nonactivated. Interestingly, in SH-SY5Y cells, light-activated [3](PF6)2 increased cell proliferation, similar to donepezil, without causing cell death. Increased Ca2+ uptake was observed, possibly via interaction with the AMPA receptor, as suggested by docking studies. These findings suggest ruthenium-based PACT compounds may serve as potential treatments for GBM, effectively attacking cancer cells while preserving healthy neuronal cells.

This minireview explores advancements in high-throughput combinatorial synthesis of metal complexes, emphasising their applications in catalysis, drug discovery, and materials science. We highlight v...

We designed a series of pseudo-octahedral arene Os(ii) complexes (Os1–Os5) with the general formula [(η6-p-cym)Os(BTAT)Cl]+, where BTAT represents chelating N^N′ ligands based on the 1-aryl-4-benzothi...