Photodynamic therapy using OR141-loaded nanovesicles for eradication of leukemic cells from ovarian tissue.

Moghassemi, Saeid [UCL] Dadashzadeh, Arezoo [UCL] Camboni, Alessandra [UCL] Feron, Olivier [UCL] Azevedo, Ricardo Bentes Andrade Amorim, Christiani [UCL]

In 2020, the estimated number of new leukemia cases was higher than 30,000 in girls between 0 and 19 years old. Due to cancer treatment, some of these patients may lose both endocrine and reproductive functions. Transplantation of cryopreserved ovarian tissue is not advised after cancer remission because it has a high risk of reintroducing malignant cells in the patient, potentially leading to leukemia recurrence. To safely transplant the ovarian tissue from these patients and restore their fertility, our goal was to develop a photodynamic therapy (PDT) strategy to eliminate leukemia ex vivo. To this end, we designed, optimized, and characterized OR141-loaded niosomes (ORN) to develop the most effective formulation for ex vivo purging ovarian fragments from chronic myelogenous leukemia cells. After establishing the best ORN formulation, the PDT efficiency of optimized ORN was determined for human ovarian stromal cells and acute myeloid leukemia cell line (HL60). Blank niosomes treatment on ovarian stromal cells causes no significant toxicity, showing that the composition of the nanoparticle is not toxic. On the other hand, the in vitro studies showed that while ovarian stromal cells were still viable (82.04 ± 2.79%) after the treatment by 0.5 µM ORN, the same treatment yielded 95.43 ± 3.89% toxicity and cell death in the cancer cells. In conclusion, our results showed that our novel PDT procedure could be a promising strategy to destroy leukemia cells in ovarian tissue fragments allowing safe transplantation in cancer survivors.