Response to the treatment of squamous cell carcinoma using photodynamic therapy in diabetic mice

Cancer remains one of the leading global health challenges and photodynamic therapy (PDT) has emerged as a promising treatment for non-melanoma skin cancer. Nevertheless, the potential influence of diabetes on the efficacy of ALA (5-aminolevulinic acid)-mediated PDT remains unclear. This study investigated the influence of type 1 diabetes (T1D) on topical ALA-PDT for squamous cell carcinoma (SCC) in Balb/c nude mice. Scratch assays with or without photobiomodulation, flow cytometry, in vivo fluorescence spectroscopy and 3D fibroblast-SCC co-cultures using Matrigel were used to evaluate wound healing, endogenous protoporphyrin IX (PpIX) production and tumor microenvironment. Photobiomodulation was performed using 810 nm LEDs in T1D-like in vitro condition with A431 cells and light fluence of 5 J/cm². Diabetes was induced in Balb/c nude mice using streptozotocin and they were considered diabetic when glycemic levels reached over 250 mg/dL, SCC tumor was grown and PDT was performed when tumor volume reached 15-25 mm³, experimental groups involved the usage of 20% ALA in cream formulation pretreated (or not) with the microneedling device, Dermaroller. Light fluence used was 30 J/cm² and animals were monitored throughout 10 days after treatment PDT. Photobiomodulation improved scratch closure under diabetic conditions after 24h. Preliminary results confirmed therapeutic efficacy and showed that microneedling enhanced ALA delivery and endogenous PpIX production. The photodynamic effect on 3D cultures showed that co-cultures were more affected than A431 individually, potentially indicating that associated the affected fibroblasts might also help eliminating tumor cells. Ongoing histological, molecular and respirometry analyses will further clarify the effects of diabetes on PDT response and tumor metabolism.

This work was supported by Coordenação de Aperfeiçoamento de Pessoa de Nível Superior (CAPES #88887.803637/2023-00 and 88887.803637/2023-00, 88881.218658/2025-01)