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.

Strategic ligand engineering is essential for the development of new photoactive transition metal complexes. One such application is the control of supramolecular, one-dimensional stacking of square-planar d8-organometallic systems. Here, we report the synthesis of a macrocyclic, tetradentate isocyanide ligand, CN4, and facile coordination to rhodium(I) yielding [Rh(CN4)][BArF4]. Single-crystal X-ray diffraction upon acetone-solution grown crystals reveals formation of a tetrameric RhI stack, constructed of two dimeric forms of monomers. UV–visible absorption spectroscopy shows two prominent absorption bands, assigned to dimer (525 nm) and tetramer (840 nm), confirming stacked species. These assignments are further supported by DOSY measurements. Solvent control over this equilibrium is achieved first with acetonitrile, favoring only tetrameric aggregation, and also with dichloromethane, disabling aggregation completely. Upon excitation, the monomeric form returns to its electronic ground state in less than 10 ns. The near-infrared-absorbing tetramer exhibits an excited state with a lifetime of 150 ns in deaerated acetonitrile and NIR-II emission at 1040 nm. This discovery provides new opportunities for innovation in photophysics and photochemistry through polynuclear architectures that exhibit emergent properties compared to traditional mononuclear transition metal complexes.

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

Après sept années de recherche, les équipes du professeur Gilles Gasser (Institute of Chemistry for Life and Health Sciences – Chimie ParisTech-PSL), en collaboration avec le Dr Marcel Hollentstein et…

Classical upconversion employs sensitizers and annihilators as two distinct molecular species and is, therefore, classified as heteromolecular. Homomolecular upconversion, the unification of both role...

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 pioneering theoretical chemist on teaching herself programming and the importance of freedom