The use of folic acid as targeting agent in PDT: what about the stability?

International audience ; Significance: Despite the conventional treatment combining chemotherapy to a cytoreductive surgery, 60% of women suffered from ovarian cancer will relapse at the end of the treatment. Indeed, our main objective is to develop a targeted PDT treatment of peritoneal carcinomatosis from ovarian cancer to improve the life expectancy of cancer patients. For this, folic acid (FA) was used as a targeting agent, which can be coupled to photosensitizers (PS) to improve the selectivity towards cancer cells that over-expressed FR-α receptors, such as ovarian cancer cells. However, FA can undergo some stability issues.Approach: We conducted a Design of Experiment (DoE to understand the parameters influencing the degradation of FA. Factors such as light, oxygen, time of storage, temperature and type of medium were evaluated FA-PS conjugates were also tested to determine the influence of PS type on the stability of FA.Results: FA-PS conjugates demonstrated different photostability, in comparison to FA. . FA-PEG-pyropheophorbide a demonstrates the best photostability. According to the DOE), after more than 80 experimental screenings, temperature, storage time and type of medium were found to be the most influencial parameters on the degradation of FA. FA moleculesalso demonstrated weaker photostability as compared to FA-PEG-pyropheophorbide a, which is an advantage for the efficiency of PDT.