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

Abstract

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.

Keywords:

• Ions interference
• biomimetic
• calcium overload
• calcium carbonate
• curcumin

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was financially supported by the National Natural Science Foundation of China (81901878, 81873188), China Postdoctoral Science Foundation (2020T130611, 2019M662553) and Key Scientific Research Projects Plan of Henan Higher Education Institutions (20A350011).