Citation: Kun Chen, Huimin Lin, Xin Peng, Ziying Wu, Jingyue Dai, Yi Sun, Yaxuan Feng, Ziyi Huang, Zhiqiang Yu, Meng Yu, Guangyu Yao, Jigang Wang. In situ synthesis of MnO₂ micro/nano-adjuvants for enhanced immunotherapy of breast tumors[J]. Chinese Chemical Letters, ;2025, 36(5): 110045. doi: 10.1016/j.cclet.2024.110045 shu

In situ synthesis of MnO₂ micro/nano-adjuvants for enhanced immunotherapy of breast tumors

Kun Chen ^{a, 1} ,
Huimin Lin ^{a, 1} ,
Xin Peng ^{d, 1} ,
Ziying Wu ^e ,
Jingyue Dai ^f ,
Yi Sun ^d ,
Yaxuan Feng ^a ,
Ziyi Huang ^a ,
Zhiqiang Yu ^c ,
Meng Yu ^{a, *,} ,
Guangyu Yao ^{b, *,} ,
Jigang Wang ^{a, g, h, i, *,}

a.
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
b.
Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510510, China
c.
Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan 523018, China
d.
Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
e.
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
f.
Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
g.
Department of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
h.
Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China
i.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

yumeng999@smu.edu.cn

yaogy@smu.edu.cn

jgwang@icmm.ac.cn

Received Date: 27 March 2024
Revised Date: 20 May 2024
Accepted Date: 22 May 2024
Available Online: 23 May 2024

Figures(4)

This study presents an approach to enhanced cancer immunotherapy through the in situ synthesis of potassium permanganate (KMnO₄) derived manganese dioxide (MnO₂) micro/nano-adjuvants. Addressing the limitations of traditional immunotherapy due to patient variability and the complexity of the tumor microenvironment, our research establishes KMnO₄ as a potent immunomodulator that enhances the efficacy of anti-programmed death-ligand 1 (αPD-L1) antibodies. The in situ synthesized MnO₂ adjuvants in the tumor exhibit direct interactions with biological systems, leading to the reduction of MnO₂ to Mn²⁺ within the tumor, and thereby improving the microenvironment for immune cell activity. Our in vitro and in vivo models demonstrate KMnO₄’s capability to induce concentration-dependent cytotoxicity in tumor cells, triggering DNA damage and apoptosis. It also potentiates immunogenic cell death by upregulating calreticulin and high mobility group box 1 (HMGB1) on the cell surface. The combination of KMnO₄ with αPD-L1 antibodies substantially inhibits tumor growth, promotes dendritic cell maturation, and enhances CD8⁺ T cell infiltration, resulting in a significant phenotypic shift in tumor-associated macrophages towards a pro-inflammatory M1 profile. Our findings advocate for further research into the long-term efficacy of KMnO₄ and its application in diverse tumor models, emphasizing its potential to redefine immune checkpoint blockade therapy and offering a new vista in the fight against cancer.
- Cancer immunotherapy,
- Potassium permanganate,
- Manganese dioxide,
- Nanoadjuvants,
- In situ synthesis
1. [1]
  B. Wang, J. Zhou, R. Li, et al., Adv. Mater. 36 (2024) 2311640. doi: 10.1002/adma.202311640
2. [2]
  Q. Li, M. Dang, J. Tao, et al., Adv. Funct. Mater. 34 (2024) 2311480. doi: 10.1002/adfm.202311480
3. [3]
  W. Zeng, Z. Li, Q. Huang, et al., Adv. Funct. Mater. 34 (2023) 2307241.
4. [4]
  D.R. Wang, X.L. Wu, Y.L. Sun, Signal Transduct. Target. Ther. 7 (2022) 331. doi: 10.1038/s41392-022-01136-2
5. [5]
  X. Wang, Y. Liu, C. Xue, et al., Nat. Commun. 13 (2022) 5685. doi: 10.1038/s41467-022-33301-0
6. [6]
  P. Sun, Z. Li, D. Zhang, et al., Chin. Chem. Lett. 35 (2024) 108346. doi: 10.1016/j.cclet.2023.108346
7. [7]
  X. Li, C. Shao, Y. Shi, W. Han, J. Hematol. Oncol. 11 (2018) 31. doi: 10.1186/s13045-018-0578-4
8. [8]
  Y. Mi, C.T. Hagan 4th, B.G. Vincent, A.Z. Wang, Adv. Sci. 6 (2019) 1801847. doi: 10.1002/advs.201801847
9. [9]
  W. Ma, R. Sun, L. Tang, et al., Adv. Mater. 35 (2023) 2303149. doi: 10.1002/adma.202303149
10. [10]
  B. Zhang, Y. Wang, S. Wang, et al., Adv. Funct. Mater. 33 (2023) 2305630. doi: 10.1002/adfm.202305630
11. [11]
  Q. Li, Z. Teng, J. Tao, et al., Small 18 (2022) 2201108. doi: 10.1002/smll.202201108
12. [12]
  L. Zhang, L. Xu, Y. Wang, et al., Chin. Chem. Lett. 33 (2022) 4089–4095. doi: 10.1016/j.cclet.2022.01.071
13. [13]
  Z. Feng, G. Chen, M. Zhong, et al., Biomaterials 302 (2023) 122333. doi: 10.1016/j.biomaterials.2023.122333
14. [14]
  D. Wei, J. Fan, J. Yan, et al., J. Am. Chem. Soc. 146 (2024) 1185–1195. doi: 10.1021/jacs.3c12706
15. [15]
  X. Sun, Y. Wang, T. Du, et al., Chin. Chem. Lett. 34 (2023) 108201. doi: 10.1016/j.cclet.2023.108201
16. [16]
  J. Wan, X. Zhang, D. Tang, T. Liu, H. Xiao, Adv. Mater. 35 (2023) e2209799. doi: 10.1002/adma.202209799
17. [17]
  B. Zhang, L. Lin, J. Mao, et al., Chin. Chem. Lett. 34 (2023) 108518. doi: 10.1016/j.cclet.2023.108518
18. [18]
  J. Wang, Q. Zhang, Y. Li, et al., Chin. Chem. Lett. 35 (2024) 108746. doi: 10.1016/j.cclet.2023.108746
19. [19]
  H. Zhu, K. Ma, R. Ruan, et al., Chin. Chem. Lett. 35 (2024) 108536. doi: 10.1016/j.cclet.2023.108536
20. [20]
  J. Gao, H. Zhang, F. Zhou, et al., Chin. Chem. Lett. 32 (2021) 1929–1936. doi: 10.1016/j.cclet.2020.12.009
21. [21]
  K. Zhang, C. Qi, K. Cai, Adv. Mater. 35 (2023) e2205409. doi: 10.1002/adma.202205409
22. [22]
  N. Jiang, Z. Zhou, W. Xiong, et al., Chin. Chem. Lett. 32 (2021) 3948–3953. doi: 10.1016/j.cclet.2021.06.053
23. [23]
  X. Sun, Y. Zhang, J. Li, et al., Nat. Nanotechnol. 16 (2021) 1260–1270. doi: 10.1038/s41565-021-00962-9
24. [24]
  M. Lv, M. Chen, R. Zhang, et al., Cell Res. 30 (2020) 966–979. doi: 10.1038/s41422-020-00395-4
25. [25]
  B. Ding, P. Zheng, P. Ma, J. Lin, Adv. Mater. 32 (2020) e1905823. doi: 10.1002/adma.201905823
26. [26]
  L. Hou, C. Tian, Y. Yan, et al., ACS Nano 14 (2020) 3927–3940. doi: 10.1021/acsnano.9b06111
27. [27]
  W. Zhang, S. Li, X. Liu, et al., Adv. Funct. Mater. 28 (2018) 1706375. doi: 10.1002/adfm.201706375
28. [28]
  S. Huang, Y. Gao, H. Li, et al., Adv. Mater. 36 (2024) e2310979. doi: 10.1002/adma.202310979
29. [29]
  T. He, X. Qin, C. Jiang, et al., Theranostics 10 (2020) 2453–2462. doi: 10.7150/thno.42981
30. [30]
  J. Azadmanesh, G.E.O. Borgstahl, Antioxidants 7 (2018) 25. doi: 10.3390/antiox7020025
31. [31]
  G. Sokhi, Br. J. Cancer 24 (1970) 290–293. doi: 10.1038/bjc.1970.33
32. [32]
  J. Tao, Y. Tian, D. Chen, et al., Angew. Chem. Int. Ed. 62 (2023) e202216361. doi: 10.1002/anie.202216361
33. [33]
  M.C. Biesinger, B.P. Payne, A.P. Grosvenor, et al., Appl. Surf. Sci. 257 (2011) 2717–2730. doi: 10.1016/j.apsusc.2010.10.051
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9. [9]
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11. [11]
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13. [13]
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14. [14]
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15. [15]
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16. [16]
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17. [17]
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18. [18]
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19. [19]
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沈阳化工大学材料科学与工程学院沈阳 110142

In situ synthesis of MnO2 micro/nano-adjuvants for enhanced immunotherapy of breast tumors

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通讯作者: 陈斌, bchen63@163.com

In situ synthesis of MnO₂ micro/nano-adjuvants for enhanced immunotherapy of breast tumors