Temoporfin

Although Boron-dipyrromethene (BODIPY) derivatives have been explored for photodynamic antibacterial or antitumor applications, respectively, dual-activity cationic BODIPY photosensitizers have received much less attention. In addition, traditional quaternary ammonium compounds (QACs) are primarily studied as antibacterial agents, with systematic reports on their direct antitumor activity remaining scarce. We developed bis-quaternary ammonium cationic BODIPY derivatives as photosensitizers to investigate dual photodynamic antibacterial/antitumor action. All synthesized new compounds demonstrated notable UV-vis absorption in the range of 646-659 nm, intense fluorescence emission (665, 670, and 675 nm), and capabilities for reactive oxygen species (ROS) generation. Among these, brominated BODIPYs II₃ and II₅ exhibited high ROS generation efficiency and significant photodynamic antitumor activity against Eca-109 cells in vitro (IC₅₀ = 0.22 μM and 0.36 μM) and in vivo, comparable to the control drug m-THPC. Compounds I₅ and II₅ demonstrated substantial photodynamic antibacterial activities against pathogenic Staphylococcus aureus (S. aureus), with minimum inhibitory concentrations (MIC) of 0.5 μg/mL for both compounds. Furthermore, they achieved effective biofilm inhibition efficiencies of 86.74% and 85.23%, respectively, through the disruption of membrane integrity. These findings hold significant promise for pioneering new multifunctional photosensitizers that enable combined or sequential antimicrobial and antitumor photodynamic therapies.

Temoporfin is a second-generation photosensitizer used in photodynamic therapy (PDT) for the clinical treatment of head and neck cancer. However, its role in inhibiting cancer cell viability under normoxic and hypoxic conditions remains unclear. The oral squamous cell carcinoma (OSCC) cell lines, SAS and OECM-1 were cultured under normoxic or hypoxic conditions to investigate temoporfin-based PDT-induced cell death and the underlying mechanisms. Cell viability was analyzed using the MTT assay. Intracellular reactive oxygen species (ROS) levels, cell apoptosis, intracellular ROS, iron levels, lipid peroxidation, and glutathione (GSH) levels were assessed by flow cytometry. The expression of proteins related to oxidative stress, apoptosis, autophagy, and ferroptosis was verified by western blotting. Results showed that increasing the temoporfin dose, absorption time, and illumination time was positively correlated with the inhibition of oral cancer cells. Hypoxic conditions attenuated the toxicity of temoporfin in cancer cells. OECM-1 cells were more sensitive to temoporfin than SAS cells. Temoporfin-based PDT-induced ROS exhibited similar trends to oxidative stress-inducing enzymes under both normoxic and hypoxic conditions and triggered cell autophagy and ferroptosis. Administration of the ferroptosis inhibitor BRD4770 under normoxic conditions reversed temoporfin-based PDT-induced reductions in glutathione peroxidase 4 (GPx4), increasing in light chain 3-II (LC3-II) and cleaved poly (ADP-ribose) polymerase (cleaved-PARP). This study confirms that hypoxia weakens the anticancer effects of temoporfin-based PDT and that ferroptosis plays a key role in temoporfin-based PDT-mediated cancer cell inhibition.