Citation: Yongzhi Wu, Rong He, Bowen Tan, Longjiang Li, Jinfeng Liao. An injectable hydrogel for chemodynamic therapy-induced ferroptosis in malignant melanoma[J]. Chinese Chemical Letters, ;2026, 37(3): 111339. doi: 10.1016/j.cclet.2025.111339 shu

An injectable hydrogel for chemodynamic therapy-induced ferroptosis in malignant melanoma

Yongzhi Wu ^{a, b, 1} ,
Rong He ^{a, b, 1} ,
Bowen Tan ^a ,
Longjiang Li ^{b, *,} ,
Jinfeng Liao ^{a, *,}

a.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
b.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

liscu1992@163.com

liaojinfeng.762@163.com

Received Date: 11 March 2025
Revised Date: 15 May 2025
Accepted Date: 16 May 2025
Available Online: 16 May 2025

Figures(4)

Chemodynamic therapy (CDT) represents a novel strategy for the safe treatment of malignant melanoma. It capitalizes on transition metal-catalyzed Fenton-like reactions to generate hydroxyl radicals (^•OH) that directly eradicate tumor cells. However, its efficacy is hindered in the tumor microenvironment (TME) by low endogenous hydrogen peroxide (H₂O₂) levels and high glutathione (GSH) content. To overcome these limitations, an injectable self-healing adipic dihydrazide (ADH)-modified hyaluronic acid (HA) (HA-ADH)/aldehyde terminated polyethylene glycol (PEG-CHO)/PVP-cupric peroxide (CuO₂) nanoparticles (HPC) hydrogel was developed. This hydrogel system is injectable, pH-responsive, self-healing, and enables sustained GSH depletion through dual Cu²⁺/^•OH-mediated mechanisms. The HPC hydrogel system not only compensates for the TME's endogenous H₂O₂ deficiency through self-generated H₂O₂ but also disrupts redox homeostasis via GSH oxidation, thereby inactivating glutathione peroxidase 4 (GPX4) and promoting lipid peroxide accumulation to trigger ferroptosis in melanoma cells. Such a strategy represents a promising approach to achieve enhanced CDT and potent ferroptosis induction by synergizing dual GSH-depleting cycling and self-sufficient H₂O₂ generation.
- Chemodynamic therapy,
- Cupric peroxide nanoparticles,
- Hydrogel,
- pH-responsive,
- Ferroptosis
1. [1]
  G.V. Long, S.M. Swetter, A.M. Menzies, et al., Lancet 402 (2023) 485–502.
2. [2]
  L. Zhai, Y. Shi, Y. Yan, et al., Chin. Chem. Lett. 34 (2023) 108104.
3. [3]
  Y. Lin, X. Wang, S. He, et al., Acta Pharm. Sin. B 14 (2024) 854–868.
4. [4]
  I. Anestopoulos, S. Kyriakou, V. Tragkola, et al., Pharmacol. Ther. 240 (2022) 108301.
5. [5]
  L. Wang, S. He, R. Liu, et al., Acta Pharm. Sin. B 14 (2024) 2263–2280.
6. [6]
  P.B. Balakrishnan, D.K. Ledezma, J. Cano-Mejia, et al., Nano Res. 15 (2022) 2300–2314. doi: 10.1007/s12274-021-3813-1
7. [7]
  S. Liang, Y. Liu, H. Zhu, et al., Exploration 4 (2024) 20230163.
8. [8]
  W. Yu, F. Jia, J. Fu, et al., ACS Nano 17 (2023) 15713–15723. doi: 10.1021/acsnano.3c02964
9. [9]
  X. Huang, T. He, X. Liang, et al., MedComm Oncol. 3 (2024) e67.
10. [10]
  D. Sheehan, K. Sheehan, J. Sheehan, J. Neurooncol. 153 (2021) 373–374. doi: 10.1007/s11060-021-03768-w
11. [11]
  N.W. Nkune, H. Abrahamse, Int. J. Mol. Sci. 22 (2021) 12549. doi: 10.3390/ijms222212549
12. [12]
  S. Sun, D. Wang, R. Yin, et al., Small 18 (2022) e2202558.
13. [13]
  P.C. Huang, E.J. Chaney, E. Aksamitiene, et al., Theranostics 11 (2021) 5620–5633. doi: 10.7150/thno.55333
14. [14]
  E.A. Thim, L.E. Kitelinger, F. Rivera-Escalera, et al., Theranostics 14 (2024) 1647–1661. doi: 10.7150/thno.92089
15. [15]
  C. Jia, Y. Guo, F.G. Wu, Small 18 (2022) e2103868.
16. [16]
  J. Tang, Y. Liu, Y. Xue, et al., Exploration 4 (2024) 20230127.
17. [17]
  Y. Zhou, S. Fan, L. Feng, et al., Adv. Mater. 33 (2021) e2104223.
18. [18]
  X. Chen, H. Yang, X. Song, et al., Chin. Chem. Lett. 34 (2023) 107753.
19. [19]
  P. Jin, X.D. Feng, C.S. Huang, et al., MedComm Oncol. 3 (2024) e70007.
20. [20]
  H. Hu, L. Yu, X. Qian, et al., Adv. Sci. 8 (2020) 2000494.
21. [21]
  L. Yuan, J. Tatineni, K.M. Mahoney, et al., Trends Immunol. 42 (2021) 209–227.
22. [22]
  C. Yin, Y. Tang, X. Li, et al., Small 14 (2018) e1703400.
23. [23]
  L.H. Fu, Y. Wan, C. Qi, et al., Adv. Mater. 33 (2021) e2006892.
24. [24]
  X. Chen, R. Kang, G. Kroemer, et al., Nat. Rev. Clin. Oncol. 18 (2021) 280–296. doi: 10.1038/s41571-020-00462-0
25. [25]
  Q. Zhou, Y. Meng, D. Li, et al., Signal Transduct. Target. Ther. 9 (2024) 55.
26. [26]
  X. Han, F. Wang, J. Shen, et al., Adv. Mater. 36 (2024) e2306993.
27. [27]
  W. Yang, Q. Zhang, J. Zhou, et al., Biomacromolecules 25 (2024) 3432–3448. doi: 10.1021/acs.biomac.4c00080
28. [28]
  L. Kahlert, E.F. Bassiony, R.J. Cox, et al., Angew. Chem. Int. Ed. 59 (2020) 5816–5822. doi: 10.1002/anie.201915486
29. [29]
  Y. Feng, Z. Zhang, W. Tang, et al., Exploration 3 (2023) 20220173.
30. [30]
  H. Xu, Z. Zhao, P. She, et al., J. Control. Release 375 (2024) 788–801.
31. [31]
  W. Zhang, Y. Shi, H. Li, et al., Carbohydr. Polym. 288 (2022) 119418.
32. [32]
  L.S. Lin, T. Huang, J. Song, et al., J. Am. Chem. Soc. 141 (2019) 9937–9945. doi: 10.1021/jacs.9b03457
33. [33]
  F.X. Wang, Z.W. Zhang, F. Wang, et al., J. Colloid Interface Sci. 649 (2023) 384–393.
34. [34]
  Y. Bian, K. Zhao, T. Hu, et al., Adv. Sci. 11 (2024) e2403791.
35. [35]
  M. Zorrón, A.L. Cabrera, R. Sharma, et al., Adv. Sci. 11 (2024) e2403204.
36. [36]
  Y. Huang, L. Mu, X. Zhao, et al., ACS Nano 16 (2022) 13022–13036. doi: 10.1021/acsnano.2c05557
37. [37]
  Y. Peng, Q.Z. Liu, D. Xu, et al., Biochem. Pharmacol. 217 (2023) 115856.
38. [38]
  M.J. Woźniak-Budych, B. Maciejewska, Ł. Przysiecka, et al., J. Mol. Liquids 319 (2020) 114086.
39. [39]
  T. Liu, B. Xiao, F. Xiang, et al., Nat. Commun. 11 (2020) 2788.
40. [40]
  S. Naz, A. Gul, M. Zia, IET Nanobiotechnol 14 (2020) 1–13. doi: 10.1049/iet-nbt.2019.0176
41. [41]
  T. Ameh, C.M. Sayes, Environ. Toxicol. Pharmacol. 71 (2019) 103220.
42. [42]
  I.C. Lee, J.W. Ko, S.H. Park, et al., Part. Fibre. Toxicol. 13 (2016) 56.
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