Citation: Ruhe Zhang, Dandan Li, Ting Liang, Xinyu Zhang, Jingyi Hou, Yang Kang, Dongjun Lin, Jun Wu. Dual redox-responsive CO₂-generating nanoparticles assembled from one-step synthesized L-cystine-based biodegradable polymers for enhanced chemotherapy of tumors[J]. Chinese Chemical Letters, ;2026, 37(7): 111680. doi: 10.1016/j.cclet.2025.111680 shu

Dual redox-responsive CO₂-generating nanoparticles assembled from one-step synthesized L-cystine-based biodegradable polymers for enhanced chemotherapy of tumors

Ruhe Zhang ^{a, 1,*,} ,
Dandan Li ^{b, 1} ,
Ting Liang ^{c, 1} ,
Xinyu Zhang ^a ,
Jingyi Hou ^d ,
Yang Kang ^{e, *,} ,
Dongjun Lin ^{a, *,} ,
Jun Wu ^{f, g, *,}

a.
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
b.
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
c.
Department of Blood Transfusion, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
d.
Department of Orthopedics and Department of Sports Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
e.
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
f.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China
g.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China

zhangrh35@mail2.sysu.edu.cn

kangy26@mail.sysu.edu.cn

lindj@mail.sysu.edu.cn

junwuhkust@ust.hk

Received Date: 12 July 2025
Revised Date: 6 August 2025
Accepted Date: 7 August 2025
Available Online: 8 August 2025

Figures(5)

Among various smart drug delivery systems (DDSs), redox-responsive systems have emerged as promising platforms for tumor therapy. Herein, we successfully fabricated a tumor microenvironment dual redox-responsive nanoparticle platform (DTX@Cys-0E NPs) assembled from an L-cystine-based biodegradable polymer (Cys-0E) for efficient delivery of docetaxel (DTX). The engineered Cys-0E features a unique structure containing both disulfide bonds and peroxalate ester bonds, synthesized via a one-step reaction. Notably, the strategic incorporation of 6-o-palmitoyl ascorbic acid (PA) not only enhances the stability of DTX@Cys-0E NPs but also generates tumor-specific H₂O₂. This PA-mediated H₂O₂ production triggers the degradation of the peroxalate ester bond, followed by CO₂ generation, which ultimately results in DTX-controlled release. Simultaneously, the disulfide bonds in Cys-0E react with high concentrations of glutathione (GSH) in tumor cells, increasing the reactive oxygen species (ROS) level, and further facilitating drug release. Both in vitro and in vivo experiment results show that, once DTX@Cys-0E NPs are enriched into tumor cells, the rapid degradation of Cys-0E triggered by these stimuli leads to a burst release of DTX, inducing tumor cell apoptosis and exhibiting significantly better tumor inhibition compared to free DTX. In summary, this novel dual redox-responsive nano platform holds great promise as a controlled drug release system for cancer therapy.
- L-Cystine,
- Dual-responsive nanoparticle,
- CO₂-generating,
- Drug delivery,
- Cancer therapy
1. [1]
  F. Bray, M. Laversanne, H. Sung, et al., CA Cancer J. Clin. 74 (2024) 229–263. doi: 10.3322/caac.21834
2. [2]
  Y. Jin, J. Jiang, W. Mao, et al., Cancer Lett. 591 (2024) 216858. doi: 10.1016/j.canlet.2024.216858
3. [3]
  A. Audisio, R. Fazio, V. Daprà, et al., Cancer Treat. Rev. 123 (2024) 102676. doi: 10.1016/j.ctrv.2023.102676
4. [4]
  M. Chalabi, Y.L. Verschoor, P.B. Tan, et al., N. Engl. J. Med. 390 (2024) 1949–1958. doi: 10.1056/nejmoa2400634
5. [5]
  C. Holohan, S. Van Schaeybroeck, D.B. Longley, et al., Nat. Rev. Cancer 13 (2013) 714–726. doi: 10.1038/nrc3599
6. [6]
  C. Frederiks, S. Lam, H. Guchelaar, et al., Cancer Treat. Rev. 41 (2015) 935–950. doi: 10.1016/j.ctrv.2015.10.010
7. [7]
  C. Zhang, L. Yan, X. Wang, et al., Nano Today 35 (2020) 101008. doi: 10.1016/j.nantod.2020.101008
8. [8]
  T.H. Baryakova, B.H. Pogostin, R. Langer, et al., Nat. Rev. Drug Discov. 22 (2023) 387–409. doi: 10.1038/s41573-023-00670-0
9. [9]
  M. Chehelgerdi, M. Chehelgerdi, O.Q.B. Allela, et al., Mol. Cancer 22 (2023) 169.
10. [10]
  W. Chen, K. Shi, Y. Yu, et al., Chin. Chem. Lett. 35 (2024) 109159. doi: 10.1016/j.cclet.2023.109159
11. [11]
  P.R. Cullis, P.L. Felgner, Nat. Rev. Drug Discov. 23 (2024) 709–722. doi: 10.1038/s41573-024-00977-6
12. [12]
  R.H. Zhang, T.Q. Nie, Y.F. Fang, et al., Biomacromolecules 23 (2022) 1–19.
13. [13]
  R. Zhang, T. Nie, L. Wang, et al., Biomater. Sci. 11 (2023) 4254–4264. doi: 10.1039/d3bm00461a
14. [14]
  D.D. Li, R.H. Zhang, G.T. Liu, et al., Adv. Healthc. Mater. 9 (2020) 2000605. doi: 10.1002/adhm.202000605
15. [15]
  Y. Liu, M. Jiang, Z. Zhao, et al., Acta Biomater. 166 (2023) 567–580. doi: 10.32604/jrm.2022.023037
16. [16]
  J. Liu, D. He, T. Hao, et al., Chin. Chem. Lett. 35 (2024) 109296. doi: 10.1016/j.cclet.2023.109296
17. [17]
  W. Zhong, X. Zhang, X. Duan, et al., Acta Biomater. 144 (2022) 67–80.
18. [18]
  S. Bai, X. Ma, X. Shi, et al., ACS Appl. Mater. Interfaces 11 (2019) 36130–36140. doi: 10.1021/acsami.9b13214
19. [19]
  C. de Gracia Lux, S. Joshi-Barr, T. Nguyen, et al., J. Am. Chem. Soc. 134 (2012) 15758–15764. doi: 10.1021/ja303372u
20. [20]
  Y.T. Chiang, Y.W. Yen, C.L. Lo, Biomaterials 61 (2015) 150–161. doi: 10.1016/j.biomaterials.2015.05.007
21. [21]
  C. Tapeinos, A. Pandit, Adv. Mater. 28 (2016) 5553–5585. doi: 10.1002/adma.201505376
22. [22]
  J. Liu, X. You, L. Wang, et al., Small 20 (2024) e2401438.
23. [23]
  X. Dong, Z. Zhang, R. Wang, et al., Small 20 (2024) e2309529. doi: 10.1002/smll.202309529
24. [24]
  R.S. Navath, Y.E. Kurtoglu, B. Wang, et al., Bioconjug. Chem. 19 (2008) 2446–2455. doi: 10.1021/bc800342d
25. [25]
  A. Russo, W. DeGraff, N. Friedman, et al., Cancer Res. 46 (1986) 2845–2848.
26. [26]
  R. Cheng, F. Feng, F. Meng, et al., J. Control. Release 152 (2011) 2–12.
27. [27]
  A. Bansal, M.C. Simon, J. Cell Biol. 217 (2018) 2291–2298. doi: 10.1083/jcb.201804161
28. [28]
  C.J. Prange, N.Y.B. Sayed, B. Feng, et al., J. Control. Release 368 (2024) 251–264.
29. [29]
  Z.Q. Zhang, X.X. Xu, J.W. Du, et al., Nat. Commun. 15 (2024) 1118. doi: 10.1038/s41467-024-44963-3
30. [30]
  F.Z. Yu, Y.L. Tu, S.W. Luo, et al., Nano Lett. 21 (2021) 2216–2223. doi: 10.1021/acs.nanolett.0c05028
31. [31]
  Z.M. Shu, I. Tanaka, A. Ota, et al., Angew. Chem. Int. Ed. 58 (2019) 6611–6615. doi: 10.1002/anie.201900993
32. [32]
  X.D. Xu, J. Wu, S.S. Liu, et al., Small 14 (2018) e1802565.
33. [33]
  J. Wu, L.L. Zhao, X.D. Xu, et al., Angew. Chem. Int. Ed. 54 (2015) 9218–9223. doi: 10.1002/anie.201503863
34. [34]
  Y. Tao, C. Dai, Z. Xie, et al., Chin. Chem. Lett. 35 (2024) 109170.
35. [35]
  L. Zhang, S. Zhang, M. Li, et al., Mater. Sci. Eng. C: Mater. Biol. Appl. 123 (2021) 111956.
36. [36]
  J. Li, W. Ke, L. Wang, et al., J. Control. Release 225 (2016) 64–74. doi: 10.17647/jss.2016.08.64.64
37. [37]
  Q. Chen, M.G. Espey, A.Y. Sun, et al., Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 8749–8754. doi: 10.1073/pnas.0702854104
38. [38]
  Q. Chen, M.G. Espey, A.Y. Sun, et al., Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 11105–11109. doi: 10.1073/pnas.0804226105
39. [39]
  H. Liu, J. Xiao, S. Wang, et al., Chem. Eng. J. 482 (2024) 149167.
40. [40]
  X. Yan, J. Bernard, F. Ganachaud, Adv. Colloid Interface Sci. 294 (2021) 102474.
41. [41]
  W. Cao, W. Wei, B. Qiu, et al., Chem. Eng. J. 483 (2024) 149187.
42. [42]
  Ⅲ M.F. Baruch, J.E. Pander, J.L. White, et al., ACS Catal. 5 (2015) 3148–3156. doi: 10.1021/acscatal.5b00402
43. [43]
  S. Mukhopadhyay, M.S. Naeem, G. Shiva Shanker, et al., Nat. Commun. 15 (2024) 3397.
44. [44]
  K.Y. Ou, X.J. Xu, S.Y. Guan, et al., Adv. Funct. Mater. 30 (2020) 1907857.
45. [45]
  C. Li, W. Jia, Z. Guo, et al., J. Mater. Chem. B 12 (2024) 800–813. doi: 10.1039/d3tb02288a
46. [46]
  S.L. Yu, R.H. Zhang, Z.X. Xie, et al., ACS Biomater. Sci. Eng. 10 (2024) 4336–4346. doi: 10.1021/acsbiomaterials.4c00345
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Dual redox-responsive CO2-generating nanoparticles assembled from one-step synthesized L-cystine-based biodegradable polymers for enhanced chemotherapy of tumors

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通讯作者: 陈斌, bchen63@163.com

Dual redox-responsive CO₂-generating nanoparticles assembled from one-step synthesized L-cystine-based biodegradable polymers for enhanced chemotherapy of tumors