Idlas Pierre, Ladaycia Abdallah, Némati Fariba, Lepeltier Elise, Pigeon Pascal, Jaouen Gerard, Decaudin Didier, Passirani Catherine
Micro et Nanomédecines Translationnelles, MINT, UNIV Angers, INSERM 1066, CNRS 6021, Angers, France.
Translational Research Department, Laboratory of preclinical Investigation, PSL University, Institut Curie, 26 rue d'Ulm, Paris 75248, France.
Int J Pharm. 2022 Oct 15;626:122164. doi: 10.1016/j.ijpharm.2022.122164. Epub 2022 Sep 8.
Ovarian cancer is one of the deadliest epithelial malignancies in women, owing to the multidrug resistance that restricts the success of conventional chemotherapy, carboplatin and paclitaxel. High grade serous ovarian carcinoma can be classified into two subtypes, the chemosensitive High OXPHOS and the Low OXPHOS tumour, less sensitive to chemotherapy. This difference of treatment efficacy could be explained by the redox status of these tumours, High OXPHOS exhibiting a chronic oxidative stress and an accumulation of reactive oxygen species. Ferrocifens, bio-organometallic compounds, are believed to be ROS producers with a good cytotoxicity on ovarian cancer cell lines. The aim of this study was to evaluate the in vivo efficacy of ferrocifen stealth lipid nanocapsules on High and Low OXPHOS ovarian Patient-Derived Xenograft models, alone or in combination to standard chemotherapy. Accordingly, two ferrocifens, P53 and P722, were encapsulated in stealth LNCs. The treatment by stealth P722-LNCs in combination with standard chemotherapy induced, with a concentration eight time lower than in stealth P53-LNCs, similar tumour reduction on a Low OXPHOS model, allowing us to conclude that P722 could be a leading ferrocifen to treat ovarian cancer. This combination of treatments may represent a promising synergistic approach to treat resistant ovarian adenocarcinoma.
卵巢癌是女性中最致命的上皮性恶性肿瘤之一，这是由于多药耐药性限制了传统化疗药物卡铂和紫杉醇的治疗效果。高级别浆液性卵巢癌可分为两种亚型，即对化疗敏感的高氧化磷酸化型和对化疗不太敏感的低氧化磷酸化型肿瘤。这些肿瘤治疗效果的差异可以通过其氧化还原状态来解释，高氧化磷酸化型表现出慢性氧化应激和活性氧的积累。二茂铁衍生物是生物有机金属化合物，被认为是活性氧的产生者，对卵巢癌细胞系具有良好的细胞毒性。本研究的目的是评估二茂铁衍生物隐形脂质纳米胶囊在高氧化磷酸化型和低氧化磷酸化型卵巢癌患者来源异种移植模型中的体内疗效，单独使用或与标准化疗联合使用。因此，将两种二茂铁衍生物P53和P722包裹在隐形脂质纳米胶囊中。在低氧化磷酸化型模型中，隐形P722脂质纳米胶囊与标准化疗联合使用时，其浓度比隐形P53脂质纳米胶囊低八倍，但能诱导相似的肿瘤缩小，这使我们得出结论，P722可能是治疗卵巢癌的主要二茂铁衍生物。这种联合治疗可能是治疗耐药性卵巢腺癌的一种有前景的协同方法。
