Metabolic intervention liposome for targeting glutamine-addiction of breast cancer.

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.