This new article publication from Acta Pharmaceutica Sinica B discusses how disrupting calcium homeostasis and glycometabolism in engineered lipid-based pharmaceuticals propel cancer immunogenic death.
Homeostasis, energy, and substance metabolism reprogramming shape various tumour microenvironments to sustain cancer stemness, self-plasticity, and treatment resistance.
Aiming at them, a lipid-based pharmaceutical loaded with CaO2 and glucose oxidase (GOx) (LipoCaO2/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism.
The loaded GOx can decompose glucose into H2O2 and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion.
The obtained gluconic acid further deprives CaO2 to produce H2O2 and release Ca2+, disrupting Ca2+ homeostasis, which synergises with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS).
Systematic experiments reveal that these sequential multifaceted events, unlocked by Ca2+ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8+ T recruitment, which results in a considerably inhibited outcome against breast cancer progression.
Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumour immune environment, which represents a significant advancement in the field of biomedical research.
Source: Compuscript Ltd