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Research Article

Metal-polyphenol-network coated CaCO3 as pH-responsive nanocarriers to enable effective intratumoral penetration and reversal of multidrug resistance for augmented cancer treatments

Ziliang Dong, Yu Hao, Quguang Li, Zhijuan Yang, Yujie Zhu, Zhuang Liu, Liangzhu Feng( )
Institute of Functional Nano & Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
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Abstract

Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance (MDR) is potent to achieve effective cancer treatment. Herein, we report a general method to synthesize pH-dissociable calcium carbonate (CaCO3) hollow nanoparticles with amorphous CaCO3 as the template, gallic acid (GA) as the organic ligand, and ferrous ions as the metallic center via a one-pot coordination reaction. The obtained GA-Fe@CaCO3 exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin, yielding drug loaded GA-Fe@CaCO3 nanotherapeutics featured in pH-responsive size shrinkage, drug release, and Fenton catalytic activity. Compared to non- responsive GA-Fe@silica nanoparticles prepared with silica nanoparticles as the template, such GA-Fe@CaCO3 confers significantly improved intratumoral penetration capacity. Moreover, both types of drug-loaded GA-Fe@CaCO3 nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA-Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate (ATP). As a result, it is found that the doxorubicin loaded GA-Fe@CaCO3 exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies. This work highlights the preparation of pH-dissociable CaCO3-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.

Keywords

self-templated synthesisgallic acid (GA)-Fe@calcium carbonate (CaCO3) hollow nanoparticlesreactive oxygen species (ROS) generation and chemodynamic therapyimproved intratumoral penetrationreversal of multi-drug resistance

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Nano Research
Volume 13 Issue 11,
November 2020
Pages 3057-3067
DOI: 10.1007/s12274-020-2972-9
Cite this article:
Dong Z, Hao Y, Li Q, et al. Metal-polyphenol-network coated CaCO3 as pH-responsive nanocarriers to enable effective intratumoral penetration and reversal of multidrug resistance for augmented cancer treatments. Nano Research, 2020, 13(11): 3057-3067. https://doi.org/10.1007/s12274-020-2972-9
Topics:
Catalyst activityCoordination reactionsDiseasesDrug deliveryNanoparticlesSilicaSilica nanoparticlesSynthesis (chemical)Tumors

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Received: 22 May 2020
Revised: 04 July 2020
Accepted: 05 July 2020
Published: 15 August 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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