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 Telagle-nastat 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.

Automated summary

This study investigated the dual inhibition of metabolic plasticity in breast cancer cells using Lip@GOx&Tel, which targeted and inhibited two nutrient supply mechanisms. This led to a reduction in ATP production and biosynthesis precursors necessary for tumor growth, resulting in anti-tumor effects. Additionally, Lip@GOx&Tel disrupted redox homeostasis, further enhancing the therapeutic effect. The study also addressed the limitation of combining protein drugs and small molecule drugs in vivo by using liposome nanoparticles. Overall, this work provides a new perspective in nanomedicine for metabolic intervention in diseases.