Targeted photodynamic therapy using a Vectorized photosensitizer coupled to folic acid analog induces ovarian tumor cell death and inhibits IL-6-mediated inflammation.

Fiche publication

Date publication

mai 2024

Journal

Journal of controlled release : official journal of the Controlled Release Society

Auteurs

Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline

Tous les auteurs :
Boidin L, Moinard M, Moussaron A, Merlier M, Moralès O, Grolez GP, Baydoun M, Mohd-Gazzali A, Tazizi MHDM, Allah HHA, Kerbage Y, Arnoux P, Acherar S, Frochot C, Delhem N

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/38789088

Résumé

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PS, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis. This PS was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PS was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα. Final PS, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PS in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φ = 0.39 and Φ = 0.53 for free Pyro-a, and Φ = 0.26 and Φ = 0.41 for PS). Any toxicity of PS was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PS on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6). This new PS has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.