Biomimetic Ca²⁺ nanogenerator based on ions interference strategy for tumour-specific therapy

Intracellular Ca²⁺ ions as second messenger played key role in cell behaviour, which was often overlooked in traditional antitumor treatment. Disrupting Ca²⁺ ion homeostasis by Ca²⁺ overload might switch ions signal from 'regulating' to 'destroying'. Inspired by this, a biomimetic Ca²⁺ 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 Ca²⁺ generation and CUR release. The CUR could further facilitate Ca²⁺ release from endoplasmic reticulum (ER) and inhibit Ca²⁺ efflux, aggravating Ca²⁺ overload to disrupt mitochondrial Ca²⁺ 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 Ca²⁺ overload therapy and chemotherapy, which would pave the way towards more effective nanotherapeutics.