Salvianolic acid B as a potent nano-agent for enhanced ALA-PDT of oral cancer and leukoplakia cells

Oral Dis. 2024 Apr;30(3):1091-1099. doi: 10.1111/odi.14525. Epub 2023 Feb 13.

Abstract

Background: Photodynamic therapy (PDT) relies on the light activation of a photosensitizers to generate reactive oxygen species such as singlet oxygen, but its effect on cancer therapy is limited dramatically by hypoxia in the tumor microenvironment.

Objectives: To determine the potential of a nano-photosensitizer loaded salvianolic acid B (SalB) and 5-aminolevulinic acid (ALA) for enhancing the efficacy of PDT in oral squamous cell carcinoma Cal27 cells and leukoplakia Leuk1 cells.

Results: Singlet oxygen sensor green (SOSG) assay showed that nano-SalB-ALA generated higher levels of singlet oxygen, compared to nano-SalB and nano-ALA. Cellular uptake assay showed that nano-SalB-ALA effectively absorbed by Leuk1 cells. Importantly, cell counting kit-8 and flow cytometry revealed that PDT with nano-SalB-ALA effectively inhibited the viability and induced the apoptosis of Cal27 and Leuk1 cells, respectively. Moreover, the tumor xenograft study revealed that PDT with nano-SalB-ALA had a stronger inhibitory effect on tumor growth of nude mice, compared to control groups.

Conclusions: The novel photosensitizer nano-SalB-ALA remarkably enhanced the efficacy of PDT by improving singlet oxygen production, inhibiting cell proliferation, promoting cell apoptosis, and suppressing tumor growth. These suggest PDT with nano-SalB-ALA could be a clinically significant and potent treatment for oral cancer and leukoplakia.

Keywords: chemopreventive agent; oral potentially malignant disorders; photodynamic therapy; salvianolic acid B; singlet oxygen.

MeSH terms

  • Aminolevulinic Acid* / pharmacology
  • Aminolevulinic Acid* / therapeutic use
  • Animals
  • Apoptosis* / drug effects
  • Benzofurans* / pharmacology
  • Benzofurans* / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line, Tumor
  • Depsides
  • Humans
  • Leukoplakia, Oral / drug therapy
  • Mice
  • Mice, Nude*
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / pathology
  • Nanoparticles
  • Photochemotherapy* / methods
  • Photosensitizing Agents* / pharmacology
  • Photosensitizing Agents* / therapeutic use
  • Singlet Oxygen / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Photosensitizing Agents
  • salvianolic acid B
  • Aminolevulinic Acid
  • Benzofurans
  • Singlet Oxygen
  • Depsides