在本研究中，合成了由不同烷基链长度（C8、C10、C12 和 C14）的脂肪酸修饰的牛酪蛋白水解肽（HP）纳米组件。使用光谱、激光粒度分析仪、接触角计、扫描电子显微镜（SEM）和冷冻透射电子显微镜（Cryo-TEM）对HP-C8-HP-C14纳米组装体的理化性质进行了表征。 HP-C8和HP-C10自组装成平均尺寸~500nm的空心立方体笼，HP-C12的组装呈现花状形貌，具有更加分散的行为，观察到液滴尺寸为~20纳米。采用CCK-8法和流式细胞术分析测试了对人乳腺癌细胞MCF-7的体外细胞毒性。 HP-Cn中HP-C12对MCF-7细胞的细胞毒性最高，抑制率为66.03%±0.35%，IC50值为7.4μM。 HP-C8、HP-C10和HP-C12对MCF-7细胞的迁移、侵袭和凋亡有显着影响。凋亡机制可能依赖于抗凋亡蛋白Bcl-2以及促凋亡蛋白Bax和caspase-8的上调。使用非靶向代谢组学通过 UHPLC-MS/MS 分析死亡的 MCF-7 细胞，揭示关键的代谢途径。版权所有 © 2023。由 Elsevier B.V. 出版。

In this study, the nano-assemblies of bovine casein hydrolyzed peptides (HP) modified by fatty acids with various alkyl chain lengths (C8, C10, C12 and C14) were synthesized. The physicochemical properties of HP-C8-HP-C14 nano-assemblies were characterized using spectra, laser particle size analyzer, contact angle meter, scanning electron microscope (SEM) and cryo-transmission electron microscope (Cryo-TEM). HP-C8 and HP-C10 self-assembled into a hollow cube cage with an average size of ~500 nm, and the assembly of HP-C12 showed a flower-shaped morphology with more dispersed behavior, and droplet size was observed as ~20 nm. The in vitro cytotoxicity against human breast cancer cells MCF-7 was tested using CCK-8 assay and flow cytometry analysis. HP-C12 showed the highest cytotoxicity for MCF-7 cells with an inhibition rate of 66.03 % ± 0.35 % with an IC50 value of 7.4 μM among HP-Cn. HP-C8, HP-C10 and HP-C12 significantly affected on the migration, invasion and apoptosis of MCF-7 cells. The apoptosis mechanism may depend on the upregulation of anti-apoptotic protein Bcl-2 as well as pro-apoptotic proteins Bax and caspase-8. The dead MCF-7 cells were analyzed with UHPLC-MS/MS using untargeted metabolomics, revealing key metabolic pathways.Copyright © 2023. Published by Elsevier B.V.