https://doi.org/10.1016/j.apsb.2024.12.018
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 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 CaO 2 and glucose oxidase (GOx) (LipoCaO 2 /GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H 2 O 2 and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO 2 to produce H 2 O 2 and release Ca 2+ , disrupting Ca 2+ 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 Ca 2+ 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.
Keywords: Calcium homeostasis disruption; Glycometabolism interference; Immunogenic cell death; Oxidative stress; Lactic acid; Engineered lipids; Starvation therapy; Cancer plasticity
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383524004751-ga1_lrg.jpg
Engineered lipid-based pharmaceuticals unlocked sequential multifaceted events to disrupt calcium homeostasis and glucose metabolism, eventually augmenting immunogenic cell death of breast cancer to repress breast cancer progression.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association .
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CiteScore: 22.4
Impact Factor: 14.8 (Top 5 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.9
ISSN 2211-3835
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Qiuxia Peng, Xiaolong Li, Chao Fang, Chunyan Zhu, Taixia Wang, Binxu Yin, Xiulin Dong, Huaijuan Guo, Yang Liu, Kun Zhang, Disrupting calcium homeostasis and glycometabolism in engineered lipid-based pharmaceuticals propel cancer immunogenic death, Acta Pharmaceutica Sinica B, Volume 15, Issue 3, 2025, Pages 1255-1267, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2024.12.018 .
Acta Pharmaceutica Sinica B