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Metabolic intervention liposome for targeting glutamine-addiction of breast cancer
Ming Wu1, Qizhi Wang2, Sai Chen1
1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Abstract:
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.
Insights
Dual inhibition of glucose and glutamine metabolism using liposome-loaded Glucose oxidase and Telaglenastat (Lip@GOx&Tel) effectively suppressed breast cancer growth and metastasis. This nanomedicine approach targets tumor cell metabolism and disrupts redox homeostasis for enhanced anti-cancer effects.
Area of Science:
- Oncology
- Nanomedicine
- Metabolic Pathways
Background:
- Tumor cells rely on glycolysis and glutamine metabolism for growth and proliferation, exhibiting metabolic plasticity.
- Metabolic compensation enables cancer cells to adapt to nutrient deprivation and therapeutic interventions.
- Targeting key metabolic pathways offers a promising strategy for cancer treatment.
Purpose of the Study:
- To investigate the dual inhibition of glycolysis and glutamine metabolism using liposome-encapsulated Glucose oxidase and Telaglenastat (Lip@GOx&Tel) against breast cancer.
- To evaluate the efficacy of Lip@GOx&Tel in reducing tumor growth and metastasis.
- To explore the potential of nanomedicine in overcoming limitations of combined drug delivery.
Main Methods:
- Liposomes were loaded with Glucose oxidase (GOx) and Telaglenastat (Tel) to create Lip@GOx&Tel nanoparticles.
- The anti-tumor and anti-metastasis effects of Lip@GOx&Tel were assessed in a 4T1 breast cancer model.
- Mechanisms including ATP production, biosynthesis precursor supply, reactive oxygen species (ROS) levels, and glutathione (GSH) levels were analyzed.
Main Results:
- Lip@GOx&Tel effectively inhibited both glycolysis and glutamine metabolism in tumor cells.
- Dual metabolic inhibition reduced ATP production and biosynthesis precursors, leading to anti-tumor and anti-metastasis effects.
- Lip@GOx&Tel treatment resulted in an 82% tumor suppression rate by up-regulating ROS and down-regulating GSH, disrupting redox homeostasis.
Conclusions:
- Lip@GOx&Tel demonstrates significant anti-cancer efficacy through dual metabolic intervention and redox homeostasis disruption.
- This study highlights the potential of liposome-based nanomedicine for combined delivery of protein and small molecule drugs in vivo.
- Metabolic intervention using nanomedicine offers a novel therapeutic strategy for breast cancer treatment.
