PDF(Pubmed)
Abstract：
2-Hydroxyoleic acid (2-OHOA) has gained attention as a membrane lipid therapy (MLT) anti-cancer drug. However, in the viewpoint of anti-cancer drug, 2-OHOA shows poor water solubility and its effectiveness still has space for improvement. Thus, this study aimed to overcome the problems by formulating 2-OHOA into liposome dosage form. Furthermore, in the context of MLT reagents, the influence of 2-OHOA on the biophysical properties of the cytoplasmic membrane remains largely unexplored. To bridge this gap, our study specifically focused the alterations in cancer cell membrane fluidity and lipid packing characteristics before and after treatment. By using a two-photon microscope and the Laurdan fluorescence probe, we noted that liposomes incorporating 2-OHOA induced a more significant reduction in cancer cell membrane fluidity, accompanied by a heightened rate of cellular apoptosis when compared to the non-formulated 2-OHOA. Importantly, the enhanced efficacy of 2-OHOA within the liposomal formulation demonstrated a correlation with its endocytic uptake mechanism. In conclusion, our findings underscore the significant influence of 2-OHOA on the biophysical properties of cancer plasma membranes, emphasizing the potential of liposomes as an optimized delivery system for 2-OHOA in anti-cancer therapy.
摘要：
2-羟基油酸（2-OHOA）作为膜脂质治疗（MLT）抗癌药物而受到关注。然而,从抗癌药物的角度来看，2-OHOA的水溶性差,其有效性仍有改进空间。因此，这项研究旨在通过将2-OHOA配制成脂质体剂型来克服这些问题。此外，在MLT试剂的背景下，2-OHOA对细胞质膜生物物理特性的影响在很大程度上仍未被探索。为了弥合这个差距，我们的研究特别关注治疗前后癌细胞膜流动性和脂质包装特征的变化。利用双光子显微镜和Laurdan荧光探针,我们注意到，脂质体掺入2-OHOA诱导更显著降低癌细胞膜流动性，与未配制的2-OHOA相比，伴随着细胞凋亡率的提高。重要的是,脂质体制剂中2-OHOA的功效增强表明与其胞吞摄取机制相关.总之,我们的发现强调了2-OHOA对癌症质膜的生物物理特性的显着影响，强调脂质体作为2-OHOA在抗癌治疗中的优化递送系统的潜力。
