Reaction Mechanism of Chemodynamic Therapy and Its Applications in Anti-Tumor Treatment

Mengyu Han; Rong Chen; Qiao Li; Hong Li; Yi Jia

doi:10.7536/PC241102

PDF(5158 KB)

Prog Chem ›› 2025, Vol. 37 ›› Issue (8) : 1091-1104. DOI: 10.7536/PC241102

Review

Reaction Mechanism of Chemodynamic Therapy and Its Applications in Anti-Tumor Treatment

Mengyu Han ¹ ,
Rong Chen ¹ ,
Qiao Li ¹ ,
Hong Li ¹^,^* ,
Yi Jia ²^,^*

Author information +

History +

Abstract

Chemodynamic therapy （CDT） refers to a method that utilizes metal ion-mediated Fenton/Fenton-like reactions to catalyze the generation of highly cytotoxic hydroxyl radicals from hydrogen peroxide，effectively killing tumor cells. It offers advantages such as tumor specificity，minimal side effects，and a treatment process initiated solely by internal tumor substances like H₂O₂ and glutathione without the need for external stimuli. However，the high concentration of glutathione in the tumor microenvironment，insufficient endogenous hydrogen peroxide，and hypoxia hinder the therapeutic effect of CDT. To enhance its effectiveness，researchers have explored various metal ion-mediated Fenton/Fenton-like reactions，leading to the proposed combination of CDT with multiple other therapies. This article reviews the reaction mechanisms of CDT and its collaborative applications with various therapies in anti-tumor treatment. It begins by discussing the catalytic reaction mechanisms of CDT mediated by different metal ions，delving into the advantages and disadvantages of various ions in catalyzing Fenton or Fenton-like reactions. Subsequently，it details the latest research progress on the combination of CDT with other therapies，such as photothermal therapy，chemotherapy，and photodynamic therapy，in anti-tumor treatments. Finally，the article proposes future research directions for the development of chemodynamic therapy and highlights key issues that need to be considered to further promote its clinical research applications.

Contents

1 Introduction

2 Mechanism for Fenton reaction mediated by various metal ions

2.1 Iron-mediated mechanism for Fenton reaction

2.2 Copper-mediated mechanism for Fenton-like reaction

2.3 Other metal ion-mediated mechanisms for Fenton-like reactions

3 CDT-based combination therapies and their anti-tumor applications

3.1 Combination therapy of PTT and CDT

3.2 Combination therapy of chemotherapy and CDT

3.3 Combination therapy of PDT and CDT

3.4 Combination therapy of other therapies and CDT

4 Conclusion and outlook

Key words

chemodynamic therapy / tumor microenvironment / oncotherapy / combination therapy

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Mengyu Han , Rong Chen , Qiao Li , et al . Reaction Mechanism of Chemodynamic Therapy and Its Applications in Anti-Tumor Treatment[J]. Progress in Chemistry. 2025, 37(8): 1091-1104 https://doi.org/10.7536/PC241102

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	Bray F, Laversanne M, Sung H, Ferlay J, Siegel R L, Soerjomataram I, Jemal A. CA A Cancer J. Clin., 2024, 74(3): 229. Cited in this article [1]

[2]	Li S L, Jiang P, Jiang F L, Liu Y. Adv. Funct. Mater., 2021, 31(22):2100243. Cited in this article [1]

[3]	Tian Q W, Xue F F, Wang Y R, Cheng Y Y, An L, Yang S P, Chen X Y, Huang G. Nano Today, 2021, 39: 101162. Cited in this article [1]

[4]	Ou R L, Aodeng G, Ai J. Pharmaceutics, 2023, 15(9): 2337. Cited in this article [1]

[5]	Sun Q Q, Wang Z, Liu B, He F, Gai S L, Yang P P, Yang D, Li C X, Lin J. Coord. Chem. Rev., 2022, 451: 214267. Cited in this article [1]

[6]	Qi J J, Jiang G Y, Wan Y Q, Liu J H, Pi F W. Chem. Eng. J., 2023, 466: 142960. Cited in this article [1]

[7]	Zhang C, Bu W B, Ni D L, Zhang S J, Li Q, Yao Z W, Zhang J W, Yao H L, Wang Z, Shi J L. Angew. Chem. Int. Ed., 2016, 55(6): 2101. Cited in this article [1]

[8]	Zhao P R, Li H Y, Bu W B. Angew. Chem. Int. Ed., 2023, 62(7): e202210415. Cited in this article [1]

[9]	Liu S Y, Hu J M. Sci. Sin.-Chim, 2020, 50(3): 366. Cited in this article [1]

[10]	Cao C Y, Wang X R, Yang N, Song X J, Dong X C. Chem. Sci., 2022, 13(4): 863. Cited in this article [1]

[11]	Wang Y F, Wang J, Chen K L, Jiao Y K, Chen T H, Wu X P, Jiang X W, Bu W B, Liu C S, Qu X. Acta Biomater., 2023, 172: 423. Cited in this article [1]

[12]	Chen F, Yang B B, Xu L, Yang J F, Li J S. ChemMedChem, 2021, 16(14): 2278. Cited in this article [4]

[13]	Wang X W, Zhong X Y, Liu Z, Cheng L. Nano Today, 2020, 35: 100946. Cited in this article [1]

[14]	Jia C Y, Guo Y X, Wu F G. Small, 2022, 18(6): 2103868. Cited in this article [1]

[15]	Zhuang Y L, Han S Y, Fang Y F, Huang H, Wu J. Coord. Chem. Rev., 2022, 455: 214360. Cited in this article [1]

[16]	Jia Y, Gao F, Wang P Z, Bai S W, Li H, Li J B. J. Colloid Interface Sci., 2024, 676: 626. Cited in this article [1]

[17]	Zhang H L, Li J J, Chen Y, Wu J Y, Wang K, Chen L J, Wang Y, Jiang X W, Liu Y Y, Wu Y L, Jin D Y, Bu W B. Adv. Mater., 2021, 33(17): 2100472. Cited in this article [1]

[18]	Tang Z M, Zhao P R, Wang H, Liu Y Y, Bu W B. Chem. Rev., 2021, 121(4): 1981. Cited in this article [2]

[19]	Zhou Y F, Fan S Y, Feng L L, Huang X L, Chen X Y. Adv. Mater., 2021, 33(48): 2104223. Cited in this article [2]

[20]	Chen X Y, Zhang H L, Zhang M, Zhao P R, Song R X, Gong T, Liu Y Y, He X H, Zhao K L, Bu W B. Adv. Funct. Mater., 2020, 30(6): 1908365. Cited in this article [3]

[21]	Wang J, Ding H Y, Zhu Y, Liu Y N, Yu M L, Cai H L, Ao R J, Huang H W, Gong P, Liao Y X, Chen Z L, Lin L S, Chen X Y, Yang H H. Angew. Chem. Int. Ed., 2023, 62(22): e202302255. Cited in this article [1]

[22]	Hao J N, Ge K M, Chen G L, Dai B, Li Y S. Chem. Soc. Rev., 2023, 52(22): 7707. Cited in this article [1]

[23]	Masomboon N, Ratanatamskul C, Lu M C. Environ. Sci. Technol., 2009, 43(22): 8629. Cited in this article [1]

[24]	Zhang H L, Chen Y, Hua W, Gu W J, Zhuang H J, Li H Y, Jiang X W, Mao Y, Liu Y Y, Jin D Y, Bu W B. Angew. Chem. Int. Ed., 2023, 62(15): e202300356. Cited in this article [1]

[25]	Tang Z M, Jiang S T, Wang Y D, Tang W L, Shu J, Zhang J Y, He H Y, Chen K J. Mater. Rep., 2023, 37(21): 75 (唐昭敏, 江舒婷, 王郁东, 唐婉兰, 舒娟, 张骥阳, 何浩洋, 陈孔军. 材料导报, 2023, 37(21): 75). Cited in this article [1]

[26]	Di X J, Pei Z C, Pei Y X, James T D. Coord. Chem. Rev., 2023, 484: 215098. Cited in this article [1]

[27]	Wang L, Xu Y T, Liu C, Si W L, Wang W J, Zhang Y W, Zhong L P, Dong X C, Zhao Y X. Chem. Eng. J., 2022, 438: 135567. Cited in this article [1]

[28]	Lu C, Zhang C, Wang P, Zhao Y, Yang Y, Wang Y J, Yuan H F, Qu S L, Zhang X B, Song G S, Pu K Y. Chem, 2020, 6(9): 2314. Cited in this article [1]

[29]	Zheng Z L, Jia Z, Qu C R, Dai R, Qin Y F, Rong S, Liu Y L, Cheng Z, Zhang R P. Small, 2021, 17(10): 2006508. Cited in this article [1]

[30]	Fu L H, Hu Y R, Qi C, He T, Jiang S S, Jiang C, He J, Qu J L, Lin J, Huang P. ACS Nano, 2019, 13(12): 13985. Cited in this article [3]

[31]	Xu X P, Li M H, Xu W J, Wang M, Wu Y, Cheng L Y, Li J Y, Qin Y, Liu S, Yang G Q, Sun K X, Zhang P. Mol. Pharmaceutics, 2024, 21(7): 3434. Cited in this article [1]

[32]	Ermak G, Davies K. Mol. Immunol., 2002, 38(10): 713. Cited in this article [1]

[33]	Northup A, Cassidy D. J. Hazard. Mater., 2008, 152(3): 1164. Cited in this article [1]

[34]	Bokare A D, Choi W. J. Hazard. Mater., 2014, 275: 121. Cited in this article [1]

[35]	Yang J, Fang L, Jiang R B, Qi L B, Xiao Y T, Wang W X, Ismail I, Fang X H. Adv. Healthc. Mater., 2023, 12(23): 2300490. Cited in this article [1]

[36]	Li H Y, Zhang H L, He X F, Zhao P R, Wu T, Xiahou J X, Wu Y L, Liu Y Y, Chen Y, Jiang X W, Lv G L, Yao Z W, Wu J, Bu W B. Adv. Mater., 2023, 35(18): 2211597. Cited in this article [1]

[37]	Li M H, Zhang W, Xu X P, Liu G Y, Dong M F, Sun K X, Zhang P. Front. Pharmacol., 2022, 13: 1065438. Cited in this article [1]

[38]	Hao Y, Dong Z L, Chen M C, Chao Y, Liu Z, Feng L Z, Hao Y, Dong Z L, Chen M C, Chao Y, Liu Z, Feng L Z. Biomaterials, 2020, 228: 119568. Cited in this article [1]

[39]	Ma S N, Li D, Jia X N, Xu W G, Ding G Y, He J Y, Wang J. Adv. Funct. Mater., 2024, 34(41): 2402692. Cited in this article [1]

[40]	Li Y C, Qian L Q, Yang Z P, Li S Y, Wu A M, Wang X X. Colloids Surf. B Biointerfaces, 2024, 239: 113911. Cited in this article [1]

[41]	Ren J, Liu C, Akhtar M H, He D, Li Y, Han W Z, Liu N, Yu C. Colloids Surf. A Physicochem. Eng. Aspects, 2024, 691: 133930. Cited in this article [1]

[42]	An D, Fu J Y, Zhang B, Xie N, Nie G H, Ågren H, Qiu M, Zhang H. Adv. Funct. Mater., 2021, 31(32): 2101625. Cited in this article [1]

[43]	Chen J J, Cao Y, Lin S Y, Niu H C, Zhang H J, Guan L, Shu C Q, Wu A J, Bian Y H, Zhu Y F. Chem. Eng. J., 2022, 431: 133466. Cited in this article [2]

[44]	Cheng H, He Y, Lu J Y, Yan Z W, Song L M, Mao Y L, Di D H, Gao Y K, Zhao Q F, Wang S L. J. Colloid Interface Sci., 2023, 639: 249. Cited in this article [2]

[45]	Wang Y R, An L, Lin J M, Tian Q W, Yang S P. Chem. Eng. J., 2020, 385: 123925. Cited in this article [2]

[46]	Wu G L, Tan X F, Yang Q L. Adv. Healthc. Mater., 2024, 13(10): 2303451. Cited in this article [1]

[47]	Huang Y J, Jiang Y L, Xiao Z H, Shen Y F, Huang L F, Xu X Y, Wei G F, Xu C J, Zhao C S. Chem. Eng. J., 2020, 380: 122369. Cited in this article [1]

[48]	Zhou G Z, Li M. Chem. Eng. J., 2022, 450: 138348. Cited in this article [2]

[49]	Zhang J J, Li Y J, Jiang M L, Qiu H Y, Li Y, Gu M E, Yin S C. ACS Biomater. Sci. Eng., 2023, 9(2): 821. Cited in this article [4]

[50]	Ou C J, Zhang Y W, Ge W, Zhong L P, Huang Y, Si W L, Wang W J, Zhao Y X, Dong X C. Chem. Commun., 2020, 56(46): 6281. Cited in this article [2]

[51]	Liu G Y, Zhu J W, Guo H, Sun A H, Chen P, Xi L, Huang W, Song X J, Dong X C. Angew. Chem. Int. Ed., 2019, 58(51): 18641. Cited in this article [2]

[52]	Fu L H, Wan Y L, Qi C, He J, Li C Y, Yang C, Xu H, Lin J, Huang P. Adv. Mater., 2021, 33(7): 2006892. Cited in this article [1]

[53]	Yang R Z, Huang B, Zhu Y T, Li Y, Liu F, Shi J. Sci. Adv., 2018, 4(12): eaat5077. Cited in this article [1]

[54]	Hang L F, Li H L, Zhang T, Men D D, Zhang C, Gao P, Zhang Q L. ACS Appl. Mater. Interfaces, 2019, 11(43): 39493. Cited in this article [1]

[55]	Xue T, Xu C N, Wang Y, Wang Y B, Tian H Y, Zhang Y C. Biomater. Sci., 2019, 7(11): 4615. Cited in this article [1]

[56]	Gao S T, Jin Y, Ge K, Li Z H, Liu H F, Dai X Y, Zhang Y H, Chen S Z, Liang X J, Zhang J C. Adv. Sci., 2019, 6(24): 1902137. Cited in this article [4]

[57]	Cai S F, Liu J M, Ding J W, Fu Z, Li H L, Xiong Y L, Lian Z, Yang R, Chen C Y. Angew. Chem. Int. Ed., 2022, 61(48): e202204502. Cited in this article [2]

[58]	Zhao D H, Li C Q, Hou X L, Wu G Y, Xie X T, Zhu D, Jin F, Zhao Y D, Liu B. Carbon, 2022, 188: 104. Cited in this article [2]

[59]	Wang N, Liu C Y, Yao W H, Wang X M, Zhou H J, Chen H L, Qiao W H. Appl. Mater. Today, 2021, 24: 101147. Cited in this article [1]

[60]	Arneth B. Medicina, 2020, 56(1): 15. Cited in this article [1]

[61]	He X L, Li M J, Fan S J, Li Y Y, Fang L, Xiang G Y, Yang T. Chem. Eng. J., 2024, 481: 148522. Cited in this article [2]

[62]	Gao Y, Zheng Q C, Xu S D, Yuan Y Y, Cheng X, Jiang S, Kenry, Yu Q H, Song Z F, Liu B, Li M. Theranostics, 2019, 9(5): 1264. Cited in this article [1]

[63]	Zhang J H, Chang L N, Hao R, Zhang G W, Liu T, Li Z K, Wang T Y, Zeng L Y. Chem. Eng. J., 2023, 474: 145485. Cited in this article [1]

[64]	Shi P F, Sun X R, Yuan H M, Chen K X, Bi S, Zhang S S. ACS Biomater. Sci. Eng., 2023, 9(10): 5441. Cited in this article [1]

[65]	Shen J, Yu H Z, Shu Y M, Ma M, Chen H R. Adv. Funct. Mater., 2021, 31(50): 2106106. Cited in this article [4]

[66]	Li S Y, Zhao L P, Zheng R R, Fan G L, Liu L S, Zhou X, Chen X T, Qiu X Z, Yu X Y, Cheng H. Part. Syst. Charact., 2020, 37(3): 1900496. Cited in this article [2]

[67]	Yang Y Q, Jiang S H, Stanciu S G, Peng H, Wu A G, Yang F. Mater. Horiz., 2024, 11(23): 5815. Cited in this article [1]

[68]	Wang Q, Qu B T, Li J, Liu Y Q, Dong J, Peng X Y, Zhang R P. ACS Appl. Mater. Interfaces, 2022, 14(4): 4980. Cited in this article [4]

[69]	Li C S, Ye J, Yang X, Liu S, Zhang Z Y, Wang J, Zhang K F, Xu J T, Fu Y J, Yang P P. ACS Nano, 2022, 16(11): 18143. Cited in this article [2]

[70]	Fu L H, Qi C, Hu Y R, Lin J, Huang P. Adv. Mater., 2019, 31(21): 1808325. Cited in this article [1]

[71]	Fang C, Deng Z, Cao G D, Chu Q, Wu Y L, Li X, Peng X S, Han G R. Adv. Funct. Mater., 2020, 30(16): 1910085. Cited in this article [1]

[72]	Guo Y X, Jia H R, Zhang X D, Zhang X P, Sun Q, Wang S Z, Zhao J, Wu F G. Small, 2020, 16(31): 2000897. Cited in this article [2]

[73]	Liang J Y, Sun Y N, Wang K L, Zhang Y W, Guo L Q, Bao Z H, Wang D, Xu H Y, Zheng J N, Yuan Y. ACS Appl. Mater. Interfaces, 2023, 15(14): 18191. Cited in this article [4]

[74]	Xu M M, Liu Y, Luo W R, Tan F R, Dong D H, Li W C, Wang L G, Yu Q Q. J. Colloid Interface Sci., 2023, 630: 804. Cited in this article [2]

[75]	Yang N, Cao C Y, Lv X Y, Zhang T, Shao J J, Song X J, Wang W J, Chen P, Huang W, Dong X C. BMEMat, 2023, 1(1): e12005. Cited in this article [1]

[76]	Yuan R T, Li Y, Wang Z H, Jia L H, Guo X, Zhou S B. Nano Today, 2023, 51: 101899. Cited in this article [1]

[77]	Chandra R A, Keane F K, Voncken F E M, Thomas C R. Lancet, 2021, 398(10295): 171. Cited in this article [1]

[78]	Atun R, Jaffray D A, Barton M B, Bray F, Baumann M, Vikram B, Hanna T P, Knaul F M, Lievens Y, Lui T. Lancet Oncol., 2015, 16(10): 1153. Cited in this article [1]

[79]	Lu M Z, Wu H A, Liu D, Wang F, Wang Y, Wang M J, Cui Q N, Zhang H, Zang F C, Ma M, Ma J, Shi F F, Zhang Y. ACS Nano, 2023, 17(23): 24170. Cited in this article [3]

[80]	Xu M M, Zhou L Q, Zheng L, Zhou Q, Liu K, Mao Y H, Song S S. Cancer Lett., 2021, 497: 229. Cited in this article [1]

[81]	Wang Y M, Wang D, Zhang Y Y, Xu H, Shen L X, Cheng J, Xu X Y, Tan H, Chen X Y, Li J S. Bioact. Mater., 2023, 22: 239. Cited in this article [2]

[82]	Xiong G L, Huang D K, Lu L F, Luo X X, Wang Y D, Liu S W, Chen M X, Yu S L, Kappen M, You C J, Lu S, Yu Y J, Lu J D, Lin F. Small Meth., 2022, 6(9): 2200379. Cited in this article [4]