A novel PDT: 5-aminolevulinic acid combined 450 nm blue laser photodynamic therapy significantly promotes cell death of HR-HPV infected cells

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):22-32. doi: 10.1080/21691401.2022.2164585.

Abstract

Human papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo, ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo.The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

Keywords: 450 nm; 5-aminolevulinic acid (5-ALA); HPV infection; cell apoptosis; photodynamic therapy; reactive oxygen species(ROS).

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Aminolevulinic Acid / therapeutic use
  • Apoptosis
  • Cell Death
  • Cell Line, Tumor
  • HeLa Cells
  • Human Papillomavirus Viruses
  • Humans
  • Lasers
  • Papillomavirus Infections* / drug therapy
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Aminolevulinic Acid
  • Photosensitizing Agents
  • Reactive Oxygen Species