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Background: Autotransplantation of cryopreserved ovarian tissue (OT) is the best alternative for preserving fertility in prepubertal girls and women who require cancer therapy immediately. However, despite its successful results, it cannot be offered to leukemia patients due to the high risk of reintroduction of malignant cells present in the cryopreserved OT. This could potentially lead to leukemia recurrence. In order to safely transplant the OT from these patients, these leukemia cells should be destroyed first. An alternative to selectively eradiate these cells without harming the follicle population could be photodynamic therapy (PDT). Compared with common strategies for cancer therapy, PDT can be specifically targeted at the tumor site. Goal: To develop a PDT strategy to purge leukemia cells ex vivo from the OT. To this end, we designed OR141-loaded niosomes (ORN) to create the most effective formulation to destroy myelogenous leukemia cells in OT fragments. Methods: In this research, response surface methodology (RSM)-based central composite design (CCD) was employed to obtain the optimized ORN formulation. After establishing the best condition, our PDT approach was used to eradicate HL60 cells from ex vivo tumor models prepared by microinjection of cancer cell suspension in ovarian fragments. Additionally, we evaluated the effect of ORN-based PDT on follicle density, survival, and tissue quality was evaluated after 7-day xenotransplantation to SCID mice. Results and discussion: The ex vivo purging of tumor models demonstrated that the PDT strategy with ORN could selectively eradicate the malignant cells from tissue fragments without affecting ovarian tissue normal cells, as evidenced by PCR and immunohistochemical analysis. Regarding the effect of our PDT approach on follicle population and OT quality, our results after xenotransplantation revealed no significant difference between the follicle density of untreated, grafted OT (unt-graft) and ORN treated OT (ORN-graft) groups (2.38 ± 0.63 and 3.21 ± 1.94 morphologically normal follicles/mm2, respectively). In addition, the results showed that the control (non-grafted OT) and ORN-graft ovarian tissue could be equally vascularized (7.65±1.45 % and 9.89±2.21 %, respectively). Moreover, the proportion of fibrotic area in control and ORN-graft groups were 15.96±5.94 % and 13.32±3.05 %, which is not significantly different from the control fragments (14.22±6.65 %). Conclusion: Our results showed that the purging procedure causes no significant impairing effect on follicles development and tissue quality, suggesting our novel PDT procedure could be a promising strategy to destroy leukemia cells in fragments of ovarian tissue allowing its safe transplantation in cancer survivors.
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Moghassemi, S., Dadashzadeh, A., & Andrade Amorim, C. (2022). Nanotechnology and photodynamic therapy for human ovarian tissue ex vivo purging. Bioregate Forum, Belgium. https://hdl.handle.net/2078.5/242718