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Nano Research 2023, 16(5): 7108-7118 https://doi.org/10.1007/s12274-022-5301-7
Research Article | Issue | Published: 14 January 2023

Mesothelin targeted nano-system enhanced chemodynamic therapy and tirapazamine chemotherapy via lactate depletion

Show Author's Information Guodong Cao1,  Wei Cao1,  Jiawei Zhang1,  Qing Chen2,  Junjie Chen1,  Qiang Chu3,  Qiang Sun4,  Maoming Xiong1( ),  Bo Chen1,5( ),  Xiang Li3( )
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 231300, China
Department of General Surgery, The Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310027, China
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, China
Jiangsu Key Laboratory of Biological Cancer, Cancer institute, Xuzhou Medical University, Xuzhou 221002, China
Department of surgery, the People’s Hospital of Hanshan County, Ma’anshan 238101, China
Keywords:
chemodynamic therapy, lactate oxidase, tumor metastasis, mesothelin, synergetic cancer therapy
Topics:
Nano biology
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Cao G, Cao W, Zhang J, et al. Mesothelin targeted nano-system enhanced chemodynamic therapy and tirapazamine chemotherapy via lactate depletion. Nano Research, 2023, 16(5): 7108-7118. https://doi.org/10.1007/s12274-022-5301-7
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Abstract Full text Electronic supplementary material About this article

The enhanced permeability and retention (EPR) effect alone is not enough for nanoparticles to reach the target. Combination of active and passive targeting may be an effective drug delivery route. Hollow ferric-tannic acid complex nanocapsules (HFe-TA) may effectively degrade and release Fe2+ ions, and Fe2+ ions induce the production of ·OH, however, the fenton reaction needs amount of H2O2 to enhance chemodynamic therapy. Due to their deficiencies, such nanoparticles cannot realize intravenous drug delivery. Here, the mesothelin-targeted membrane (MTM) was constructed to realize accurate delivery nano-system, and mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM. Lactate oxidase (Lox) was loaded on HFe-TA to obtain Lox@HFe-TA. Lox@HFe-TA was coated with MTM to develop the MTM nanosystem. Tirapazamine (TPZ) therapy also requires hypoxia circumstance. The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro. We also tested the biological safety of the treatment. In this study, we overcame the EPR defects via the MTM nanosystem, which can realize acute targeted delivery to the tumour site, lactate depletion, promoted reactive oxygen species (ROS) induction, and enhanced the effect of TPZ, demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.


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Abstract
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Electronic supplementary material
About this article

Mesothelin targeted nano-system enhanced chemodynamic therapy and tirapazamine chemotherapy via lactate depletion

Show Author's information Guodong Cao1, Wei Cao1, Jiawei Zhang1, Qing Chen2, Junjie Chen1, Qiang Chu3, Qiang Sun4, Maoming Xiong1( ), Bo Chen1,5( ), Xiang Li3( )
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 231300, China
Department of General Surgery, The Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310027, China
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, China
Jiangsu Key Laboratory of Biological Cancer, Cancer institute, Xuzhou Medical University, Xuzhou 221002, China
Department of surgery, the People’s Hospital of Hanshan County, Ma’anshan 238101, China

Abstract

The enhanced permeability and retention (EPR) effect alone is not enough for nanoparticles to reach the target. Combination of active and passive targeting may be an effective drug delivery route. Hollow ferric-tannic acid complex nanocapsules (HFe-TA) may effectively degrade and release Fe2+ ions, and Fe2+ ions induce the production of ·OH, however, the fenton reaction needs amount of H2O2 to enhance chemodynamic therapy. Due to their deficiencies, such nanoparticles cannot realize intravenous drug delivery. Here, the mesothelin-targeted membrane (MTM) was constructed to realize accurate delivery nano-system, and mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM. Lactate oxidase (Lox) was loaded on HFe-TA to obtain Lox@HFe-TA. Lox@HFe-TA was coated with MTM to develop the MTM nanosystem. Tirapazamine (TPZ) therapy also requires hypoxia circumstance. The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro. We also tested the biological safety of the treatment. In this study, we overcame the EPR defects via the MTM nanosystem, which can realize acute targeted delivery to the tumour site, lactate depletion, promoted reactive oxygen species (ROS) induction, and enhanced the effect of TPZ, demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.

Keywords: chemodynamic therapy, lactate oxidase, tumor metastasis, mesothelin, synergetic cancer therapy

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Publication history
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Acknowledgements

Publication history

Received: 29 July 2022
Revised: 31 October 2022
Accepted: 07 November 2022
Published: 14 January 2023
Issue date: May 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

This work was supported by the mission book of promotion program of basic and clinical collaborative research of Anhui Medical University (No. 2022xkjT028), Anhui Provincial Scientific Research Preparation Plan Project (No. 2022AH051171), the Anhui Provincial Natural Science Foundation (No. 2208085MH240), Postgraduates of Colleges and Universities in Anhui Province (No. YJS20210308), the National Natural Science Foundation of China (No. 81602425), the Anhui Quality Engineering Project (Nos. 2020jyxm0898, 2020jyxm0910, and 2019kfkc334), the Anhui Medical University Clinical Research Project (No. 2020xkj176), the Anhui Health Soft Science Research Project (No. 2020WR01003), and the Key Research and Development Program of Anhui Province (No. 201904a07020045).

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