@article{Dong2020, 
author = {Ziliang Dong and Yu Hao and Quguang Li and Zhijuan Yang and Yujie Zhu and Zhuang Liu and Liangzhu Feng},
title = {Metal-polyphenol-network coated CaCO3 as pH-responsive nanocarriers to enable effective intratumoral penetration and reversal of multidrug resistance for augmented cancer treatments},
year = {2020},
journal = {Nano Research},
volume = {13},
number = {11},
pages = {3057-3067},
keywords = {self-templated synthesis, gallic acid (GA)-Fe@calcium carbonate (CaCO3) hollow nanoparticles, reactive oxygen species (ROS) generation and chemodynamic therapy, improved intratumoral penetration, reversal of multi-drug resistance},
url = {https://www.sciopen.com/article/10.1007/s12274-020-2972-9},
doi = {10.1007/s12274-020-2972-9},
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.}
}