Citation: Meng Pan, Dong Mo, Wen Chen, Yun Yang, Qingya Liu, Yujia Wei, Xicheng Li, Hanzhi Deng, Yan Yu, Liping Yuan, Yu Liu, Zhiyong Qian. Ultrasound-augmented chemodynamic and chemotherapy amplify cascade oxidative stress for potentiating immunogenic cell death in pancreatic cancer treatment[J]. Chinese Chemical Letters, ;2026, 37(9): 112846. doi: 10.1016/j.cclet.2026.112846 shu

Ultrasound-augmented chemodynamic and chemotherapy amplify cascade oxidative stress for potentiating immunogenic cell death in pancreatic cancer treatment

Meng Pan ^a ,
Dong Mo ^b ,
Wen Chen ^a ,
Yun Yang ^c ,
Qingya Liu ^d ,
Yujia Wei ^a ,
Xicheng Li ^a ,
Hanzhi Deng ^a ,
Yan Yu ^e ,
Liping Yuan ^{a, f} ,
Yu Liu ^a ,
Zhiyong Qian ^{a, *,}

a.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
b.
Department of Radiology, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
c.
Research Laboratory of Plastic and Burns Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
d.
Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
e.
Department of Chemistry, Xihua University, Chengdu 610039, China
f.
Chongqing Institute for Food and Drug Control, Chongqing 401121, China

zhiyongqian@scu.edu.cn

Received Date: 13 February 2026
Revised Date: 24 April 2026
Accepted Date: 27 April 2026
Available Online: 27 April 2026

Figures(8)

Pancreatic cancer (PCa) is highly aggressive and resistant to conventional therapies due to its dense stroma and immunosuppressive microenvironment. To overcome these barriers, we engineered dextran-coated copper peroxide-doxorubicin nanoclusters (DCPD NCs) that enabled ultrasound (US)-augmented chemodynamic therapy (CDT) and chemotherapy. In the acidic tumor microenvironment, DCPD NCs disassemble and co-release Cu²⁺, doxorubicin, and self-supplied H₂O₂. Cu²⁺ depletes glutathione (GSH) and catalyzes H₂O₂ to generate ^•OH with US (1.5 fold higher than that without US). Under US treatment, DCPD NCs not only increased the permeability of Panc02 tumor spheroids, but also increased intracellular reactive oxygen species by 2.1 times, depleted GSH by up to 25.2%, and induced lipid peroxidation. This nanoplatform works synergistically to induce potent immunogenic cell death. In both subcutaneous and orthotopic PCa mice models, this nanoplatform demonstrated remarkable therapeutic effects. The tumor weights of mice treated with DCPD NCs + US were significantly reduced by 91.8% and 85.7% vs. controls, with robust calreticulin (CRT) exposure and HMGB1 translocation in tumors. This work establishes an US augmented and self-reinforcing nanoplatform that overcomes stromal and metabolic barriers in PCa, providing a synergistic strategy for catalytic immunotherapy.
- Pancreatic cancer,
- Reactive oxygen species,
- Chemotherapy,
- Chemodynamic therapy,
- Ultrasound,
- Immunogenic cell death
1. [1]
  T.F. Stoop, A.A. Javed, A. Oba, et al., Lancet 405 (2025) 1182–1202. doi: 10.1016/S0140-6736(25)00261-2
2. [2]
  C.J. Halbrook, C.A. Lyssiotis, M. Pasca di Magliano, A. Maitra, Cell 186 (2023) 1729–1754. doi: 10.1016/j.cell.2023.02.014
3. [3]
  P.P. Provenzano, C. Cuevas, A.E. Chang, et al., Cancer Cell 21 (2012) 418–429. doi: 10.1016/j.ccr.2012.01.007
4. [4]
  M.A. Jacobetz, D.S. Chan, A. Neesse, et al., Gut 62 (2013) 112–120. doi: 10.1136/gutjnl-2012-302529
5. [5]
  H. Wang, L. Qi, Y.F. Fang, et al., J. Control. Release 388 (2025) 114278. doi: 10.1016/j.jconrel.2025.114278
6. [6]
  L.J. Peng, Y.F. Liang, X.N. Guo, et al., Nanoscale Adv. 7 (2025) 5888–5904. doi: 10.1039/d5na00513b
7. [7]
  J. Yang, R. Kato, J. Choi, Nanoscale 17 (2025) 22715–22732. doi: 10.1039/d5nr01067e
8. [8]
  Q.Y. Deng, A. Hua, Q.F. Zhao, et al., Biomaterials 324 (2026) 123501. doi: 10.1016/j.biomaterials.2025.123501
9. [9]
  P.P. Yang, X. Zhi, Y.X. Xu, et al., Nano Today 51 (2023) 101891. doi: 10.1016/j.nantod.2023.101891
10. [10]
  J.R. Cui, Z.H. Xue, Z.X. Zhang, et al., Adv. Funct. Mater. 36 (2025) e20855.
11. [11]
  N.C. Song, G.Q. Tian, H.J. Li, et al., Nano Lett. 25 (2025) 17693–17701. doi: 10.1021/acs.nanolett.5c04676
12. [12]
  Z. Hu, J. Meng, MedComm Biomater. Appl. 4 (2025) e70034.
13. [13]
  P.R. Zhao, H.Y. Li, W.B. Bu, Angew. Chem. Int. Ed. 65 (2025) e22670.
14. [14]
  C. Zhang, W.B. Bu, D.L. Ni, et al., Angew. Chem. Int. Ed. 55 (2016) 2101–2106. doi: 10.1002/anie.201510031
15. [15]
  P.H. Wei, X.G. Niu, D.L. Wang, et al., Mater. Today Bio 32 (2025) 101913. doi: 10.1016/j.mtbio.2025.101913
16. [16]
  X.L. Cai, Q.H. Zheng, Y. Wu, et al., Chin. Chem. Lett. 37 (2026) 111670. doi: 10.1016/j.cclet.2025.111670
17. [17]
  L.P. Zhao, C.Y. Huang, R.R. Zheng, et al., MedComm Biomater. Appl. 4 (2025) e70024.
18. [18]
  L.S. Lin, T. Huang, J. Song, et al., J. Am. Chem. Soc. 141 (2019) 9937–9945. doi: 10.1021/jacs.9b03457
19. [19]
  L. Yu, W.Q. Han, J. Zhang, et al., Chem. Eng. J. 520 (2025) 166043. doi: 10.1016/j.cej.2025.166043
20. [20]
  W.W. Wu, Y. Yang, Y. Zhang, et al., Chem. Eng. J. 481 (2024) 148113. doi: 10.1016/j.cej.2023.148113
21. [21]
  H.R. Zhu, C.Q. Huang, J.R. Di, et al., ACS Nano 17 (2023) 12544–12562. doi: 10.1021/acsnano.3c02401
22. [22]
  Y.L. Fang, S.S. Huang, Q.Y. Hu, et al., ACS Nano 17 (2023) 24883–24900. doi: 10.1021/acsnano.3c05898
23. [23]
  Y. He, X. Tian, M. Zhang, et al., Biomater. Sci. 12 (2024) 5534–5546. doi: 10.1039/d4bm00930d
24. [24]
  S.X. Hou, Y.E. Gao, X.B. Ma, et al., Chem. Eng. J. 416 (2021) 129037. doi: 10.1016/j.cej.2021.129037
25. [25]
  Y.X. Xiong, Z.T. Yong, S.Y. Li, et al., Adv. Funct. Mater. 34 (2023) 2310158.
26. [26]
  L. Zhao, Y.W. Chen, Q.L. Wei, et al., Chem. Eng. J. 492 (2024) 152265. doi: 10.1016/j.cej.2024.152265
27. [27]
  A.H. Zhang, W.C. Kong, X.L. Zhang, et al., Nanoscale 17 (2025) 7760–7771. doi: 10.1039/d4nr04944f
28. [28]
  G.T. Tan, C.Y. Qi, Q.Q. Zhang, et al., J. Control. Release 376 (2024) 899–912. doi: 10.1016/j.jconrel.2024.10.072
29. [29]
  X.W. Wen, C.X. Wang, S.H. Bi, et al., Small 20 (2024) 2405457. doi: 10.1002/smll.202405457
30. [30]
  Q.Q. Sun, Z. Wang, B. Liu, et al., Coord. Chem. Rev. 451 (2022) 214267. doi: 10.1016/j.ccr.2021.214267
31. [31]
  Q.Y. Zhao, Y.C. Zhao, S.J. Zhong, et al., Chin. Chem. Lett. 35 (2024) 109644. doi: 10.1016/j.cclet.2024.109644
32. [32]
  L.P. Yuan, M. Pan, H.Z. Deng, et al., Chin. Chem. Lett. 36 (2025) 110723. doi: 10.1016/j.cclet.2024.110723
33. [33]
  M. Li, X. Lan, X.M. Han, et al., ACS Appl. Mater. Interfaces. 13 (2021) 29269–29280. doi: 10.1021/acsami.1c03409
1. [1]
  Li Qin , Wenjing Wei , Keqing Wang , Xianbao Shi , Guixia Ling , Peng Zhang . Ultrasound-responsive heterojunction sonosensitizers for multifunctional synergistic sonodynamic therapy. Chinese Chemical Letters, 2025, 36(7): 110777-. doi: 10.1016/j.cclet.2024.110777
2. [2]
  Qinyu Zhao , Yunchao Zhao , Songjing Zhong , Zhaoyang Yue , Zhuoheng Jiang , Shaobo Wang , Quanhong Hu , Shuncheng Yao , Kaikai Wen , Linlin Li . Urchin-like piezoelectric ZnSnO₃/Cu₃P p-n heterojunction for enhanced cancer sonodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109644-. doi: 10.1016/j.cclet.2024.109644
3. [3]
  Xin Li , Fei Xiong , Xudong Cao , Wei Liu , Haobo Chen , Jiayu He , Weina Zhang , Longguang Tang , Wei Huang , Xikuang Yao . CD44-targeting and ZIF-8 gated gold nanocage for programmed breast cancer therapy through Pt-induced immunogenic cell death. Chinese Chemical Letters, 2026, 37(1): 110970-. doi: 10.1016/j.cclet.2025.110970
4. [4]
  Zhongyu Wang , Lijun Wang , Huaixin Zhao . DNA-based nanosystems to generate reactive oxygen species for nanomedicine. Chinese Chemical Letters, 2024, 35(11): 109637-. doi: 10.1016/j.cclet.2024.109637
5. [5]
  Kun-Heng Li , Hong-Yang Zhao , Dan-Dan Wang , Ming-Hui Qi , Zi-Jian Xu , Jia-Mi Li , Zhi-Li Zhang , Shi-Wen Huang . Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death. Chinese Chemical Letters, 2024, 35(5): 108882-. doi: 10.1016/j.cclet.2023.108882
6. [6]
  Xiaoyu Fan , Ergui Luo , Wenjuan Wang , Zhi Du , Yi Deng , Di Huang . Nanozyme-armed probiotics: Mastering redox modulation for synergistic therapy. Chinese Chemical Letters, 2026, 37(9): 112058-. doi: 10.1016/j.cclet.2025.112058
7. [7]
  Xueying Shi , Xiaoxuan Zhou , Bing Xiao , Hongxia Xu , Wei Zhang , Hongjie Hu , Shiqun Shao , Zhuxian Zhou , Youqing Shen , Xiaodan Xu , Jianbin Tang . A β-lapachone-loaded iron-polyphenol nanocomplex enhances chemodynamic therapy through cascade amplification of ROS in tumor. Chinese Chemical Letters, 2025, 36(5): 110178-. doi: 10.1016/j.cclet.2024.110178
8. [8]
  Zekun Gao , Xiuli Zheng , Weimin Liu , Jie Sha , Shuaishuai Bian , Haohui Ren , Jiasheng Wu , Wenjun Zhang , Chun-Sing Lee , Pengfei Wang . GSH-activatable copper-elsinochrome off-on photosensitizer for combined specific NIR-Ⅱ two-photon photodynamic/chemodynamic therapy. Chinese Chemical Letters, 2025, 36(3): 109874-. doi: 10.1016/j.cclet.2024.109874
9. [9]
  Dou Zhang , Xinyi Cai , Yimin Li , Yong Liu , Long Qiu , Zhenying Diao , Xuyi Liu , Yuta Nishina , Yajuan Zou , Jianbo Sun , Shujing Liang , Daxiang Cui , Ting Yin . Nanozyme with dual enzyme activity mediating cascade catalytic therapy synergize multiple functions for antitumor therapy. Chinese Chemical Letters, 2026, 37(3): 111569-. doi: 10.1016/j.cclet.2025.111569
10. [10]
  Yanjun Cai , Yong Jiang , Yu Chen , Erzhuo Cheng , Yuan Gu , Yuwei Li , Qianqian Liu , Jian Zhang , Jifang Liu , Shisong Han , Bin Yang . Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy. Chinese Chemical Letters, 2025, 36(5): 110437-. doi: 10.1016/j.cclet.2024.110437
11. [11]
  Xiaoyi Meng , Xinyue Sun , Zhaogang Sun , Yue Cheng , Yong Wang , Jun Ye , Yin Xiao , Hongqian Chu . Supramolecular-orchestrated carrier-free chemodynamic synergists with augmented oxidative damage for potentiated cancer therapy. Chinese Chemical Letters, 2025, 36(5): 110765-. doi: 10.1016/j.cclet.2024.110765
12. [12]
  Wenbin Zhou , Yafei Gao , Xinyu Feng , Yanqing Zhang , Cong Yang , Lanxi He , Fenghe Zhang , Xiaoguang Li , Qing Li . Biomimetic nanoplatform integrates FRET-enhanced photodynamic therapy and chemotherapy for cascaded revitalization of the tumor immune microenvironment in OSCC. Chinese Chemical Letters, 2025, 36(1): 109763-. doi: 10.1016/j.cclet.2024.109763
13. [13]
  Xinlu Zhang , Yongxin Liu , Huan Li , Shutong Chen , Guocheng Wang , Xu Zhang , Chen Cao , Xiaoyuan Chen , Sheng Wang . A hypoxia-activated copper ion nanoexchanger for cancer immunotherapy by in situ precise production of immunogenic cell death inducer. Chinese Chemical Letters, 2026, 37(3): 111404-. doi: 10.1016/j.cclet.2025.111404
14. [14]
  Zhi Li , Shuya Pan , Yuan Tian , Shaowei Liu , Weifeng Wei , Jinlin Wang , Tianfeng Chen , Ling Wang . Selenium nanoparticles enhance the chemotherapeutic efficacy of pemetrexed against non-small cell lung cancer. Chinese Chemical Letters, 2024, 35(12): 110018-. doi: 10.1016/j.cclet.2024.110018
15. [15]
  Xiaoyan Liu , Cong Xu , Ruhe Zhang , Yilu Zheng , Hengyu Liu , Haolin Chen , Meng Zhao , Jun Wu , Dongjun Lin . Black phosphorus nanosheets-based platform for B-cell lymphoma chemo-photothermal therapy. Chinese Chemical Letters, 2026, 37(5): 111401-. doi: 10.1016/j.cclet.2025.111401
16. [16]
  Xiaoli Cai , Qihui Zheng , Yu Wu , Xin Cheng , Chengzhou Zhu . H₂O₂ self-supplying cascade catalysis based on single-atom Cu nanozyme for augmented cancer therapy. Chinese Chemical Letters, 2026, 37(4): 111670-. doi: 10.1016/j.cclet.2025.111670
17. [17]
  Haijing Cui , Weihao Zhu , Chuning Yue , Ming Yang , Wenzhi Ren , Aiguo Wu . Recent progress of ultrasound-responsive titanium dioxide sonosensitizers in cancer treatment. Chinese Chemical Letters, 2024, 35(10): 109727-. doi: 10.1016/j.cclet.2024.109727
18. [18]
  Huanhui Wang , Longyi Nan , Yan Zheng , Jianpeng Guo , Guangchun Piao . HOF-based catalytic platform combining sonodynamic therapy and bioorthogonal activation of immunosuppression reversal for cancer therapy. Chinese Chemical Letters, 2026, 37(8): 111837-. doi: 10.1016/j.cclet.2025.111837
19. [19]
  Yunyan Li , Zimin Cai , Zhicheng Wang , Sifeng Zhu , Wendian Liu , Cheng Wang . Construction of biomimetic hybrid nanovesicles based on M1 macrophage-derived exosomes for therapy of cancer. Chinese Chemical Letters, 2025, 36(4): 109942-. doi: 10.1016/j.cclet.2024.109942
20. [20]
  Ning Tian , Haoyu Ju , Qian Hu , Qifeng Hou , Yiping Lu , Yu Liu , Jinmei Huang , Zhong-Hong Zhu , Bin Zhang , Jin Huang , Ming-Hua Zeng . Solvothermal domino synthesis of an ER-targeted iron(Ⅱ) complex for inducing immunogenic cell death. Chinese Chemical Letters, 2026, 37(6): 111038-. doi: 10.1016/j.cclet.2025.111038

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(11)
HTML views(2)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142