Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
School of Stomatology, Shandong University, Jinan, PR China.
J Drug Target. 2021 Dec;29(10):1094-1101. doi: 10.1080/1061186X.2021.1919123. Epub 2021 May 3.
Intracellular Ca ions as second messenger played key role in cell behaviour, which was often overlooked in traditional antitumor treatment. Disrupting Ca ion homeostasis by Ca overload might switch ions signal from 'regulating' to 'destroying'. Inspired by this, a biomimetic Ca nanogenerator was constructed. Briefly, the curcumin (CUR) was loaded into mesoporous calcium carbonate nanoparticles (MCC NPs), and then coated with platelet (PLT) membrane. Upon reaching tumour cells by PLT membrane-mediated tumour targeting effect, PLT@MCC/CUR would instantaneously decompose in acidic lysosomes, concurrently accompanying with Ca generation and CUR release. The CUR could further facilitate Ca release from endoplasmic reticulum (ER) and inhibit Ca efflux, aggravating Ca overload to disrupt mitochondrial Ca homeostasis for mitochondria apoptosis signalling pathway activation. Interestingly, such effect was ineffective in normal cells, realising the tumour-specific therapeutic therapy. Based on ions interference strategy, PLT@MCC/CUR herein offered synergistic combination of Ca overload therapy and chemotherapy, which would pave the way towards more effective nanotherapeutics.
细胞内钙离子作为第二信使在细胞行为中发挥着关键作用，但在传统的抗肿瘤治疗中往往被忽视。通过钙超载破坏钙离子稳态，可能会使离子信号从“调节”转变为“破坏”。受此启发，构建了一种仿生钙纳米发电机。简而言之，将姜黄素 (CUR) 装载到介孔碳酸钙纳米颗粒 (MCC NPs) 中，然后用血小板 (PLT) 膜进行包覆。当通过 PLT 膜介导的肿瘤靶向作用到达肿瘤细胞时，PLT@MCC/CUR 会在酸性溶酶体中瞬间分解，同时伴随着钙的产生和 CUR 的释放。CUR 还可以进一步促进内质网 (ER) 中钙的释放并抑制钙外流，加剧钙超载，破坏线粒体钙稳态，激活线粒体凋亡信号通路。有趣的是，这种作用在正常细胞中无效，实现了肿瘤特异性治疗。基于离子干扰策略，PLT@MCC/CUR 提供了钙超载治疗和化疗的协同组合，为更有效的纳米治疗铺平了道路。
