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Research Article

CaCO3-MnSiOx hybrid particles to enable CO2-mediated combinational tumor therapy

Congkun Xie1,§Tian Zhang1,§Yike Fu1,2( )Gaorong Han1Xiang Li1,2( )
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China
ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China

§ Congkun Xie and Tian Zhang contributed equally to this work.

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Graphical Abstract

1. Novel hybrid particles (CaCO3@MS) were constructed to enable agitated promotion of CO2, Mn2+, and Ca2+ in tumor cells and local pH modulation through a single platform.2. With the treatment of CaCO3@MS, the cellular oxidative damage mediated by a novel mechanism of “exogenous CO2 enhanced catalytic therapy”, functions collaboratively with intracellular calcium enrichment, leading to remarkable tumor inhibition phenomenon.

Abstract

Nanocatalysts mediated reactive oxygen species (ROS) based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects. However, the treatment outcome is limited by the efficiency of local catalytic reaction. Herein, we report a novel type of core–shell hybrid nanoparticles (CaCO3@MS), consisting of CaCO3 and MnSiOx, for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload. In this system, MnSiOx serves as catalysts with glutathione (GSH) responsive Mn2+ ions release functionality. CaCO3 nanoparticles play three important roles, including carbon dioxide (CO2) donor, pH modulator, and Ca2+ overload agent. It is found that the CaCO3 nanoparticles can induce CO2 production and pH increase in acidic tumor environment, both of which promote Mn2+ mediated ROS generation. And simultaneous release of Ca2+ ions from CaCO3 triggers calcium overload in tumor, which functions collaboratively with excessive ROS to induce cancer cell apoptosis. The results demonstrate that after treatment with CaCO3@MS, a remarkable tumor inhibition was achieved both in vitro and in vivo, while no clear toxic effect was observed. This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an “exogenous CO2 delivery” strategy for combinational tumor therapy.

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Nano Research
Pages 8281-8290
Cite this article:
Xie C, Zhang T, Fu Y, et al. CaCO3-MnSiOx hybrid particles to enable CO2-mediated combinational tumor therapy. Nano Research, 2022, 15(9): 8281-8290. https://doi.org/10.1007/s12274-022-4471-7
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Received: 08 March 2022
Revised: 22 April 2022
Accepted: 25 April 2022
Published: 14 June 2022
© Tsinghua University Press 2022
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