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.
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