International Journal of Nanomedicine (Jun 2022)

Research Progress on Improving the Efficiency of CDT by Exacerbating Tumor Acidification

  • Chen W,
  • Liu J,
  • Zheng C,
  • Bai Q,
  • Gao Q,
  • Zhang Y,
  • Dong K,
  • Lu T

Journal volume & issue
Vol. Volume 17
pp. 2611 – 2628

Abstract

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Wenting Chen,1 Jinxi Liu,1 Caiyun Zheng,1 Que Bai,1 Qian Gao,1 Yanni Zhang,1 Kai Dong,2 Tingli Lu1 1Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, 710072, People’s Republic of ChinaCorrespondence: Tingli Lu, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of China, Tel/Fax +86 29 8846 0332, Email [email protected] Kai Dong, School of Pharmacy, Xi’an Jiaotong University, Xi’an, 710072, People’s Republic of China, Tel/Fax +86 29-82655139, Email [email protected]: In recent years, chemodynamic therapy (CDT) has received extensive attention as a novel means of cancer treatment. The CDT agents can exert Fenton and Fenton-like reactions in the acidic tumor microenvironment (TME), converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). However, the pH of TME, as an essential factor in the Fenton reaction, does not catalyze the reaction effectively, hindering its efficiency, which poses a significant challenge for the future clinical application of CDT. Therefore, this paper reviews various strategies to enhance the antitumor properties of nanomaterials by modulating tumor acidity. Ultimately, the performance of CDT can be further improved by inducing strong oxidative stress to produce sufficient ·OH. In this paper, the various acidification pathways and proton pumps with potential acidification functions are mainly discussed, such as catalytic enzymes, exogenous acids, CAIX, MCT, NHE, NBCn1, etc. The problems, opportunities, and challenges of CDT in the cancer field are also discussed, thereby providing new insights for the design of nanomaterials and laying the foundation for their future clinical applications.Graphical Abstract: Keywords: chemodynamic therapy, Fenton/Fenton-like reactions, tumor microenvironment, reactive oxygen specie

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