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CaCO3 nanoparticles incorporated with KAE to enable amplified calcium overload cancer therapy
Biomaterials ( IF 14.0 ) Pub Date : 2021-08-22 , DOI: 10.1016/j.biomaterials.2021.121080
Yonglu Li 1 , Su Zhou 1 , Haizhao Song 2 , Ting Yu 1 , Xiaodong Zheng 1 , Qiang Chu 1
Affiliation  

Calcium overload therapy has attracted widespread attention in oncological field, whereas its efficacy has been limited due to insufficient calcium ions in tumor site and poor efficiency of calcium entering tumor, resulting in dissatisfied therapeutic effect. Kaempferol-3-O-rutinoside (KAE), a biosafe flavone with excellent anti-cancer ability, can effectively disrupt calcium homeostasis regulation and facilitate calcium influx, while calcium carbonate (CaCO3) serves as an ideal calcium ions supplier. Inspired by these concepts, KAE loaded into CaCO3 nanoparticles and incorporated with the cancer cell membrane (M) for synergistic tumor therapy. In this therapeutic platform (M@CaCO3@KAE), membrane coating ensures targeted delivery of CaCO3@KAE. Upon reaching tumor, CaCO3@KAE specifically responds to tumor microenvironment, consequently releases KAE and calcium ions. KAE effectively breaks the calcium balance, while calcium ions remarkably aggravate and magnify KAE-mediated calcium overload. Accordingly, mitochondrial structure and functions are destructed, causing cytoskeleton collapse and oxidative stress, leading to cancerous cellular apoptosis. With the combined and cascaded efficacy, considerable in vitro and in vivo tumor inhibition was achieved by M@CaCO3@KAE. This study provides an alternative nano-system, acting as a biomimetic calcium bomb, to ensure targeted, synergistic, efficient and biosafe calcium overload tumor therapy.



中文翻译:

与 KAE 结合的 CaCO3 纳米粒子可实现放大的钙超载癌症治疗

钙超载疗法在肿瘤学领域受到广泛关注,但由于肿瘤部位钙离子不足,钙进入肿瘤的效率低,导致疗效不理想。Kaempferol-3-O-rutinoside (KAE) 是一种具有优异抗癌能力的生物安全黄酮,可有效破坏钙稳态调节并促进钙内流,而碳酸钙 (CaCO 3 ) 则是理想的钙离子供应商。受这些概念的启发,KAE 加载到 CaCO 3纳米粒子中并与癌细胞膜 (M) 结合以进行协同肿瘤治疗。在这个治疗平台 (M@CaCO 3 @KAE) 中,膜涂层确保 CaCO 3 的靶向递送@凯。到达肿瘤后,CaCO 3 @KAE 特异性响应肿瘤微环境,从而释放 KAE 和钙离子。KAE 有效打破钙平衡,而钙离子显着加剧和放大 KAE 介导的钙超载。因此,线粒体结构和功能被破坏,导致细胞骨架崩溃和氧化应激,导致癌细胞凋亡。凭借组合和级联功效,M@CaCO 3 @KAE实现了相当大的体外体内肿瘤抑制。这项研究提供了一种替代纳米系统,充当仿生钙炸弹,以确保靶向、协同、高效和生物安全的钙过载肿瘤治疗。

更新日期:2021-09-03
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