Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy.

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

Induction of Immunogenic Cell Death by Photodynamic Therapy Mediated by Aluminum-Phthalocyanine in Nanoemulsion.

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs-CRT, HSP70, HSP90, HMGB1, and IL-1ß-were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.