Modified 5-aminolevulinic acid photodynamic therapy reduces pain and improves therapeutic effects in cutaneous squamous cell carcinoma mouse model

Lasers Surg Med. 2022 Jan 23. doi: 10.1002/lsm.23516. Online ahead of print.


Background and objectives: Conventional ALA-PDT (C-PDT) has limited efficacy in cutaneous squamous cell carcinoma (cSCC), and there is obvious pain during treatment, which limits its clinical application. We sought to modify photodynamic therapy into a more painless and effective treatment.

Methods: We modified C-PDT by reducing the incubation time of the pro-sensitizer and increasing the light dose; we named this method modified ALA-PDT (M-PDT). We compared the pain response and curative effect between C-PDT and M-PDT in cSCC mouse models. Pain-related proteins were examined by western blot analysis and immunohistochemistry. Tumor progression-associated signaling pathways were analyzed by RNA-seq and western blot analysis. Reactive oxygen species (ROS) generation was measured with a ROS test kit and Microplate reader.

Results: M-PDT greatly reduced pain during treatment. Interestingly, when the cSCC tumor volume increased to 150-200 mm3 , M-PDT almost completely eliminated the tumors, while C-PDT did not. The better curative effect of M-PDT might be due to the stronger suppression of the Stat3, Erk1/2, and mTOR signaling pathways. Moreover, flow cytometry demonstrated that M-PDT could recruit CD8+ T cells to inhibit cSCC progression. Further investigation determined that the different mechanisms of C-PDT and M-PDT were related to more ROS generation induced by M-PDT.

Conclusions: Our results suggest that M-PDT, which is more painless and effective than C-PDT, is expected to provide a solution for the treatment of cSCC.

Keywords: conventional 5-aminolevulinic acid photodynamic therapy; cutaneous squamous cell carcinoma; modified 5-aminolevulinic acid photodynamic therapy; pain.