Disrupting calcium homeostasis and glycometabolism in engineered lipid-based pharmaceuticals propel cancer...

Area of Science:

• Biomedical Research
• Cancer Therapy
• Drug Delivery Systems

Background:

• Tumor microenvironments reprogram metabolism to promote cancer stemness and treatment resistance.
• Disrupting homeostasis and metabolism are key strategies to overcome cancer's adaptability.

Purpose of the Study:

• To develop a lipid-based pharmaceutical (LipoCaO2/GOx, LCG) to disrupt calcium homeostasis and interfere with cancer cell glycometabolism.
• To investigate the synergistic effects of calcium disruption and metabolic interference on breast cancer progression and the tumor immune microenvironment.

Main Methods:

• Formulation of a lipid-based pharmaceutical encapsulating calcium peroxide (CaO2) and glucose oxidase (GOx).
• In vitro and in vivo experiments to assess the impact of LCG on calcium homeostasis, glycometabolism, reactive oxygen species (ROS) production, and immune cell infiltration.
• Evaluation of anti-tumor efficacy in a breast cancer model.

Main Results:

• LCG effectively disrupted calcium homeostasis and interfered with glucose metabolism by inhibiting lactic acid secretion.
• The treatment led to glutathione depletion, increased ROS production, and enhanced cancer immunogenic cell death.
• LCG inhibited regulatory T cell (Treg) infiltration and promoted CD8+ T cell recruitment, leading to significant inhibition of breast cancer progression.

Conclusions:

• The developed LCG strategy effectively combines ion interference and starvation therapy to disrupt cancer cell homeostasis and metabolism.
• This approach creates an anti-tumor immune environment, highlighting its potential for effective breast cancer treatment.
• The findings represent a significant advancement in biomedical research for cancer therapy.