Cai Liqin, Shao Xiang, Mao Xinghuai, Fu Yaming, Yang Qian
School of Advanced Manufacturing, Fuzhou University, Jinjiang, Fujian 362200, China.
School of Advanced Manufacturing, Fuzhou University, Jinjiang, Fujian 362200, China.
Int J Biol Macromol. 2025 Jan;286:138427. doi: 10.1016/j.ijbiomac.2024.138427. Epub 2024 Dec 9.
Triple negative breast cancer (TNBC) seriously endangers women's life and health due to its high invasion and mortality. Reactive oxygen species (ROS) mediated tumor cells apoptosis is considered an effective anticancer approach. Herein, we designed a natural active triple helix β-Glucan (BFP) wrapped single walled carbon nanotubes (SWNTs)-loaded doxorubicin (DOX) self-assembly (BSD) via generating excess ROS to induce oxidative stress damage for TNBC therapy. BSD could directly consume glutathione (GSH) to promote ROS. In vitro results demonstrated that BSD exhibited obvious antitumor effects to breast cancer cells by promoting apoptosis. Un-targeted metabolomics under molecular level identified the specific metabolic targets and unveiled that BSD markedly disturbed multiple metabolic pathways, including purine metabolism, pentose phosphate pathway, glutathione metabolism pathways, amino sugar and nucleotide sugar metabolism and energy metabolism, led to the inhibition of DNA and RNA synthesis, the generation of ROS, the exacerbation of DNA damage, the disruption of cell membrane integrity and the decrease of ATP. In vitro and in vivo oxidative stress assays further verified that BSD significantly promoted intracellular oxidative stress and resulted in cell damage. This study provides theoretical basis for the development and screening of new drugs based on ROS therapy for TNBC.
三阴性乳腺癌（TNBC）因其高侵袭性和死亡率严重危及女性的生命健康。活性氧（ROS）介导的肿瘤细胞凋亡被认为是一种有效的抗癌方法。在此，我们设计了一种天然活性三螺旋β-葡聚糖（BFP）包裹的负载阿霉素（DOX）的单壁碳纳米管（SWNTs）自组装体（BSD），通过产生过量ROS诱导氧化应激损伤来治疗TNBC。BSD可直接消耗谷胱甘肽（GSH）以促进ROS生成。体外实验结果表明，BSD通过促进细胞凋亡对乳腺癌细胞表现出明显的抗肿瘤作用。分子水平的非靶向代谢组学确定了特定的代谢靶点，并揭示BSD显著扰乱了多个代谢途径，包括嘌呤代谢、磷酸戊糖途径、谷胱甘肽代谢途径、氨基糖和核苷酸糖代谢以及能量代谢，导致DNA和RNA合成受到抑制、ROS生成、DNA损伤加剧、细胞膜完整性破坏以及ATP减少。体外和体内氧化应激实验进一步证实，BSD显著促进细胞内氧化应激并导致细胞损伤。本研究为基于ROS疗法的TNBC新药研发和筛选提供了理论依据。
