Efficient Synthesis of Chlorin e6 and Its Potential Photodynamic Immunotherapy in Mouse Melanoma by the Abscopal Effect

Int J Mol Sci. 2023 Feb 15;24(4):3901. doi: 10.3390/ijms24043901.

Abstract

Photodynamic therapy (PDT) can eradicate not only cancer cells but also stimulate an antitumor immune response. Herein, we describe two efficient synthetic methodologies for the preparation of Chlorin e6 (Ce6) from Spirulina platensis and address the phototoxic effect of Ce6 in vitro along with antitumor activity in vivo. Melanoma B16F10 cells were seeded and phototoxicity was monitored by the MTT assay. The C57BL/6 mice were subcutaneously inoculated on the left and right flank with B16F10 cells. The mice were intravenously injected with Ce6 of 2.5 mg/kg and then exposed to red light (660 nm) on the left flank tumors 3 h after the injection. The immune response was studied by analyzing Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and Interleukin-2 (IL-2) of the right flank tumors through qPCR. Our results revealed that the tumor was suppressed not only in the left flank but also in the right flank, where no PDT was given. The upregulated gene and protein expression of IFN-γ, TNF-α, and IL-2 revealed antitumor immunity due to Ce6-PDT. The findings of this study suggest an efficient methodology of Ce6 preparation and the efficacy of Ce6-PDT as a promising antitumor immune response.

Keywords: Chlorin e6; antitumor activity; immune response; photodynamic therapy; photosensitizer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chlorophyllides* / chemical synthesis
  • Chlorophyllides* / therapeutic use
  • Immunotherapy / methods
  • Interleukin-2
  • Melanoma, Experimental* / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • Photochemotherapy* / methods
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / therapeutic use
  • Tumor Necrosis Factor-alpha

Substances

  • Chlorophyllides
  • Interleukin-2
  • Photosensitizing Agents
  • phytochlorin
  • Tumor Necrosis Factor-alpha