Disrupting calcium homeostasis and glycometabolism in engineered lipid-based pharmaceuticals propel cancer immunogenic death.
10.1016/j.apsb.2024.12.018
- Author:
Qiuxia PENG
1
;
Xiaolong LI
2
;
Chao FANG
1
;
Chunyan ZHU
1
;
Taixia WANG
1
;
Binxu YIN
1
;
Xiulin DONG
1
;
Huaijuan GUO
1
;
Yang LIU
1
;
Kun ZHANG
1
Author Information
1. Central Laboratory and Department of Medical Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
2. Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai 200032, China.
- Publication Type:Journal Article
- Keywords:
Calcium homeostasis disruption;
Cancer plasticity;
Engineered lipids;
Glycometabolism interference;
Immunogenic cell death;
Lactic acid;
Oxidative stress;
Starvation therapy
- From:
Acta Pharmaceutica Sinica B
2025;15(3):1255-1267
- CountryChina
- Language:English
-
Abstract:
Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment 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 synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical 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 receives 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-tumor immune environment, which represents in the field of biomedical research.
