细胞外
细胞质
细胞生物学
钙
化学
线粒体
癌细胞
细胞凋亡
生物物理学
生物化学
生物
癌症
遗传学
有机化学
作者
Zhenghao Zhang,Xuan Sun,Yinghao Ding,Xiangyang Zhang,Yiming Zhang,Tianxiao Zhang,Jie Liu,Ling Wang,Zhimou Yang,Zhiwen Hu
出处
期刊:Nano Today
[Elsevier]
日期:2023-10-01
卷期号:52: 101974-101974
被引量:2
标识
DOI:10.1016/j.nantod.2023.101974
摘要
Calcium (Ca2+) overload therapy is an efficient cancer treatment modality that increases aberrant cytoplasmic Ca2+ accumulation and activates mitochondrial apoptotic cascades. Current strategies primarily use exogenous inorganic Ca2+ salts to generate these effects. However, off-target Ca2+ release and the resulting hypercalcemic crisis limit their applications. We here report our serendipitous finding that a self-assembling peptide of Nap-GFFpYHWYGYTPQNVI (namely N-pGE11), possessing both alkaline phosphatase (ALP)-responsive and epidermal growth factor receptors (EGFR) binding properties, can mobilize the extracellular Ca2+ reservoir for Ca2+ overload therapeutics. N-pGE11 is capable of producing the EGFR-specific nanofibers on HeLa cell membranes in an ALP-responsive manner, which then facilitates extracellular Ca2+ influx and accumulation in the cytoplasm by indirectly stimulating TRP channels. Cytoplasmic Ca2+ overload is transmitted to the mitochondria, thus generating mitochondrial stress and caspase-3-dependent apoptosis. Meanwhile, excess cytoplasmic Ca2+ is also transported into the extracellular space and then results in thorough cell calcification via the secretion of Ca2+-enriched vesicles through exocytotic pathways. Consequently, N-pGE11 effectively inhibits tumor growth with good biocompatibility, whereas its therapeutic efficacy is enhanced significantly by feeding mice a high-calcium diet.
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