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

Abstract

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 mm 3 , 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.

Modified 5-aminolevulinic acid photodynamic therapy suppresses cutaneous squamous cell carcinoma through blocking Akt/mTOR-mediated autophagic flux

“…We previously clarified that M-PDT is painless and effective in cSCC treatment (Liu et al, 2021;Zeng et al, 2022c), but the underlying inhibitory mechanism remains unclear. The relationship between cell death and autophagy has been widely reported (Gao et al, 2020).…”

“…ROS production is essential for the function of M-PDT (Zeng et al, 2022c). We wanted to know whether M-PDT-induced autophagy is ROS-dependent.…”

“…The pain is a key factor limiting efficacy during ALA-PDT. We previously modified conventional ALA-PDT by reducing the ALA incubation time, and increasing the light dose, then we found that this modified ALA-PDT (M-PDT) not only reduced pain but also had acceptable therapeutic effect in severe acne vulgaris (Zhang et al, 2021), condylomata acuminata (Zhang et al, 2020) and cSCC (Liu et al, 2021;Zeng et al, 2022c). However, the molecular mechanism of M-PDT in cSCC remains unclear.…”

Modified painless photodynamic therapy for facial multiple actinic keratosis in China: A prospective split‐face control study

“…As well as we observed that the lesion clearance rate of M‐PDT reached 100% clearance earlier than C‐PDT for Grade I lesions and a higher clearance rate for Grade II lesions. M‐PDT was comparable to C‐PDT in treating multiple AK on the face, similar to animal models 20 . Based on a mouse model of squamous cell carcinoma treated with M‐PDT, M‐PDT produced more cumulative ROS than C‐PDT during treatment.…”

“…Surprisingly, M‐PDT has shown excellent efficacy and reduced pain in treating moderate to severe acne vulgaris and condyloma acuminatum 18,19 . What is more, M‐PDT with accumulative higher dose illumination was even more effective than C‐PDT for larger cSCC tumors in animal studies 20 …”