The growth and rapid proliferation of tumor cells depend on both glycolysis and glutamine metabolism, leading to metabolic compensation. Here, dual inhibition on the metabolic plasticity by Glucose oxidase and Telaglenastat loaded liposome (Lip@GOx&Tel) were studied for intervening metabolic pathway on energy and material against breast cancer. Lip@GOx&Tel targeting inhibited the two nutrient supply mechanisms employed by tumor cells, reducing the supply of ATP production and biosynthesis precursors essential necessary for tumor, thereby eliciting anti-tumor and anti-metastasis effect. Meanwhile, Lip@GOx&Tel ingeniously amplify the therapeutic effect by up-regulating ROS and down-regulating GSH to disrupt redox homeostasis, thus resulting in inspiring 82% tumor suppression rate on 4 T1 tumor model. Moreover, our study solved the limitation of combination between protein drugs and small molecule drugs in vivo by using liposome nanoparticles with clinical translation value. In short, this work provides a unique perspective of nanomedicine for treating diseases from metabolic intervention.

肿瘤细胞的生长和快速增殖依赖于糖酵解和谷氨酰胺代谢，导致代谢补偿。在这里，研究了葡萄糖氧化酶和装载 Telaglenastat 的脂质体 (Lip@GOx&Tel) 对代谢可塑性的双重抑制，以干预针对乳腺癌的能量和材料的代谢途径。Lip@GOx&Tel 靶向抑制肿瘤细胞采用的两种营养供应机制，减少肿瘤必需的 ATP 产生和生物合成前体的供应，从而引发抗肿瘤和抗转移作用。同时，Lip@GOx&Tel 巧妙地通过上调 ROS 和下调 GSH 以破坏氧化还原稳态来放大治疗效果，从而在 4 T1 肿瘤模型上实现 82% 的肿瘤抑制率。而且，在体内通过使用具有临床转化价值的脂质体纳米粒子。简而言之，这项工作为通过代谢干预治疗疾病的纳米医学提供了独特的视角。