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Nano Research 2022, 15(5): 4334-4343 https://doi.org/10.1007/s12274-022-4069-0
Research Article | Issue | Published: 29 January 2022

Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance

Show Author's Information Zhimin Tian1,§,  Junlong Zhao2,§,  Shoujie Zhao3,§,  Huicheng Li4,  Zhixiong Guo1,  Zechen Liang1,  Jiayuan Li1,  Yongquan Qu1( ),  Dongfeng Chen5( ),  Lei Liu5( )
Department Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an 710072, China
State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an 710032, China
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing 400042, China

§ Zhimin Tian, Junlong Zhao, and Shoujie Zhao contributed equally to this work.

Keywords:
nanozyme, Ca2+ nano-inhibitor , nanoceria, tumor drug resistance, phytic acid
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Tian Z, Zhao J, Zhao S, et al. Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance. Nano Research, 2022, 15(5): 4334-4343. https://doi.org/10.1007/s12274-022-4069-0
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Abstract Full text Electronic supplementary material About this article

Ca2+ plays critical roles in the development of diseases, whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency. To solve this issue, with the help of Ca overexpressed tumor drug resistance model, the phytic acid (PA)-modified CeO2 nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+ inhibitor to successfully reverse tumor drug resistance through Ca2+ negative regulation strategy. Using doxorubicin (Dox) as a model chemotherapeutic drug, the Ca2+ nano-inhibitors efficiently deprived intracellular excessive free Ca2+, suppressed P-glycoprotein (P-gp) expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells. This Ca2+ negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects. Besides, nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice. We anticipate that this safe and effective Ca2+ negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors, improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca2+ associated diseases.


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Electronic supplementary material
About this article

Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance

Show Author's information Zhimin Tian1,§, Junlong Zhao2,§, Shoujie Zhao3,§, Huicheng Li4, Zhixiong Guo1, Zechen Liang1, Jiayuan Li1, Yongquan Qu1( ), Dongfeng Chen5( ), Lei Liu5( )
Department Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an 710072, China
State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an 710032, China
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing 400042, China

§ Zhimin Tian, Junlong Zhao, and Shoujie Zhao contributed equally to this work.

Abstract

Ca2+ plays critical roles in the development of diseases, whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency. To solve this issue, with the help of Ca overexpressed tumor drug resistance model, the phytic acid (PA)-modified CeO2 nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+ inhibitor to successfully reverse tumor drug resistance through Ca2+ negative regulation strategy. Using doxorubicin (Dox) as a model chemotherapeutic drug, the Ca2+ nano-inhibitors efficiently deprived intracellular excessive free Ca2+, suppressed P-glycoprotein (P-gp) expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells. This Ca2+ negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects. Besides, nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice. We anticipate that this safe and effective Ca2+ negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors, improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca2+ associated diseases.

Keywords: nanozyme, Ca2+ nano-inhibitor , nanoceria, tumor drug resistance, phytic acid

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Publication history
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Publication history

Received: 26 October 2021
Revised: 03 December 2021
Accepted: 13 December 2021
Published: 29 January 2022
Issue date: May 2022

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