Figures & data
Figure 1. Discovery of immunogenic cell death (ICD)-promoting ruthenium (Ru)-based photosensitizers (PS)
(a). Structural features of novel Ru PSs. Nine different compounds were synthesized and characterized to determine the impact of the ligand combinations on the photophysical properties and PDT efficacies within this new Ru PS class. The combination of tpbn or dnp as the chromophoric NNN ligand, dppn as the PDT ligand, and 4-pic or 4-mp as the monodentate L ligand produced the optimal energetics for singlet and triplet states to yield NIR-active Ru PSs. We identified ML18H01 as a lead Ru PSs for further in vivo studies. (b). Induction of ICD in melanoma following Ru-based photodynamic therapy (PDT). The Ru PS absorbs photons from a light source, initially forming the short-lived excited singlet state that undergoes a change in electron spin to produce the long-lived and lower-energy triplet state. The triplet state PS produces reactive oxygen species (ROS) which leads to B16F10 cancer cell death. This Ru PS-based PDT additionally induces the expression of molecules associated with inflammatory pathways and damage-associated molecular patterns (DAMPs) characteristic of immunogenic cell death. In vivo vaccination of mice with Ru PDT-treated melanoma cells develop antigen-specific antitumor immunity protective against melanoma growth and confirm the induction of ICD. IL6: Interleukin 6; IFNβ: Interferon Beta; IFIT1: Interferon Induced Protein With Tetratricopeptide Repeats 1; TLR3: Toll-Like Receptor 3; HSP90: Heat Shock Protein 90; HSPA1B: Heat Shock Protein Family A (Hsp70) Member 1B; CXCL10: C-X-C Motif Chemokine Ligand 10; TNFα: Tumor Necrosis Factor-Alpha; H2D: H-2 class I histocompatibility antigen, D chain; β2M: Beta-2-Microglobulin; TAP1: Transporter associated with Antigen Processing 1; CALR: Calreticulin; ATP: Adenosine triphosphate; HMGB1: High Mobility Group Box 1.
