卵巢癌（OC）是女性中最致命的癌症之一。由于微小肿瘤残留物的存在而导致腹膜频繁复发，这证明了开发新疗法的合理性。事实上，我们的主要目标是开发一种针对 OC 腹膜癌病的靶向光动力疗法 (PDT) 治疗方法，以提高癌症患者的预期寿命。在此，我们提出了一种靶向PDT，使用矢量光敏剂（PS）与新的叶酸类似物（FAA）（称为PSFAA）结合，以靶向腹膜转移上过度表达的叶酸受体α（FRα）。该 PSFAA 是焦脱镁叶绿酸-a (Pyro-a) 作为 PS 通过聚乙二醇 (PEG) 间隔基与新合成的 FAA 偶联的结果。与低表达 FRα 的纤维肉瘤细胞相比，在两种过表达 FRα 的人类 OC 细胞系上评估了 PSFAA 的选择性和 PDT 功效。最终的PSFAA，包括新FAA的合成及其与Pyro-a的缀合，经过10个合成步骤得到，总产率为19%。对 PSFAA 在 EtOH 中的光物理性质进行了测试，结果显示与游离 Pyro-a 相似，例如荧光和单线态氧量子产率（游离 Pyro-a 的 Φf=0.39 和 ΦΔ=0.53，Φf=0.26 和 ΦΔ=0.41对于 PSFAA）。注意到 PSFAA 的任何毒性。光照后，PS 浓度和光剂量呈现剂量依赖性效应。此外，检测到 PSFAA 对 OC 细胞分泌组的 PDT 功效可诱导促炎细胞因子分泌 (IL-6) 减少。这种新的 PSFAA 显示出有前景的生物学特性，突出了该疗法的选择性，为治疗陷入治疗困境的癌症开辟了新的视角。版权所有 © 2024。由 Elsevier B.V. 出版。

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 PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis. This PSFAA 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 PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα. Final PSFAA, 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 PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6). This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.Copyright © 2024. Published by Elsevier B.V.