Yi Jiadai, Wang Huan, Deng Qingqing, Huang Congcong, Zhang Lu, Sun Mengyu, Ren Jinsong, Qu Xiaogang
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun Jilin 130022 P. R. China
School of Applied Chemistry and Engineering, University of Science and Technology of China Hefei Anhui 230026 P. R. China.
Chem Sci. 2025 Feb 28;16(14):6014-6022. doi: 10.1039/d4sc06481j. eCollection 2025 Apr 2.
Cancer cells exhibit altered metabolism and energetics, prominently reprogramming lipid metabolism to support tumor growth and progression, making it a promising target for cancer therapy. However, traditional genetic and pharmaceutical approaches for disrupting lipid metabolism face challenges due to the adaptability of tumor metabolism and potential side effects on normal tissues. Here, we present a bacteria-based bioorthogonal platform combining transition metal catalysts and to disrupt the flexible lipid homeostasis in tumors. This platform activates glutamine transporter inhibitors , targeting lipid synthesis in hypoxic tumor environments, while inhibits lipid accumulation. By disrupting lipid metabolism and glutamine utilization, the present study proposes a safe and potent strategy for cancer therapy, with potential applications for other metabolic diseases.
癌细胞表现出代谢和能量学的改变，显著地重新编程脂质代谢以支持肿瘤生长和进展，使其成为癌症治疗的一个有前景的靶点。然而，由于肿瘤代谢的适应性以及对正常组织的潜在副作用，传统的破坏脂质代谢的基因和药物方法面临挑战。在此，我们提出一种基于细菌的生物正交平台，该平台结合过渡金属催化剂来破坏肿瘤中灵活的脂质稳态。这个平台激活谷氨酰胺转运体抑制剂，靶向缺氧肿瘤环境中的脂质合成，同时抑制脂质积累。通过破坏脂质代谢和谷氨酰胺利用，本研究提出了一种安全有效的癌症治疗策略，对其他代谢性疾病也有潜在应用。
