AlPc/ZnPc-based oncological photodynamic therapy for a selective eradication of leukemic cells from ovarian tissue

Photodiagnosis Photodyn Ther. 2021 Dec:36:102555. doi: 10.1016/j.pdpdt.2021.102555. Epub 2021 Sep 28.

Abstract

Due to the risk of reintroducing malignant cells, autotransplantation of cryopreserved ovarian tissue is not allowed in leukemia patients. In order to restore fertility in these patients, ex vivo purging of ovarian fragments could be proposed as a strategy to eradicate malignant cells before grafting. Photodynamic therapy (PDT), as a clinical-approved modality, is a minimally invasive and selective therapeutic for eliminating malignant cells. The present work aims therefore to evaluate the phototoxicity of two photosensitizers (aluminum phthalocyanine (AlPc) and zinc phthalocyanine (ZnPc)) on leukemia cells. To this end, two lines of malignant cells (K562 and HL-60) and isolated ovarian stromal cells (control) were treated by PDT using a diode laser with various energy densities. Cell viability after the treatment, the amount of generated reactive oxygen species, dark toxicity of the photosensitizers, and single-cell morphology were studied. Our results demonstrated that using irradiation with the energy density of 10 J/cm2, 1 µM AlPc could significantly reduce the viability of K562 (4.73 ± 0.14%) and HL-60 (2.74 ± 0.31%). Similarly, the viability of these cells was reduced (K562 cells: 3.84 ± 0.81%; HL-60 cells: 6.82 ± 3.21%) with 1 µM ZnPc and an energy density of 50 J/cm2. On the other hand, these PDT protocols had no significant effect on stromal cells. These findings indicate that our approach can be a promising strategy for the safe restoration of fertility in leukemia patients. However, further studies are necessary to assess its efficiency in ovarian fragments containing malignant cells to determine their eradication rate and the effect of our treatment on the survival of stromal cells and preantral follicles.

Keywords: Cancer therapy; Leukemia; Ovarian transplantation; Photodynamic therapy; Photoimmunotherapy; Photosensitizer; Phthalocyanine.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Indoles
  • Organometallic Compounds*
  • Photochemotherapy* / methods
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Zinc

Substances

  • Indoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • aluminum phthalocyanine
  • Zinc