Citation: Shuang Liang, Jianjun Yao, Dan Liu, Mengli Zhou, Yong Cui, Zhaohui Wang. Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy[J]. Chinese Chemical Letters, ;2025, 36(3): 109856. doi: 10.1016/j.cclet.2024.109856 shu

Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy

Shuang Liang ^{a, c, 1} ,
Jianjun Yao ^{a, b, 1} ,
Dan Liu ^{a, c} ,
Mengli Zhou ^{a, c} ,
Yong Cui ^{b, *,} ,
Zhaohui Wang ^{a, c, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
b.
School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 110016, China
c.
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

fayongcui@163.com

zhaohuiwang@imm.ac.cn

Received Date: 9 February 2024
Revised Date: 28 March 2024
Accepted Date: 2 April 2024
Available Online: 3 April 2024

Figures(6)

The cyclic guanosine monophosphate-adenosine monophosphate synthase and the stimulator of interferon genes (cGAS-STING) has emerged as a promising target for cancer immunotherapy. However, the development of natural STING agonists is impeded by several challenges, including limited biostability, poor pharmacokinetics, and inefficient cytosolic delivery. Herein, we meticulously designed a double-layer polyethylenimine (PEI) modified nanoscale covalent organic polymer (CPGP) for efficient delivery of 2′3′ cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a natural STING agonist. The double-layer PEI structured CPGP enhanced both the loading capacity and stability of cGAMP. Furthermore, CPGP improved the intracellular delivery efficiency and amplified the activation of STING pathway for the secretion of type-Ⅰ interferon and pro-inflammatory cytokines. In contrast, single-layered nanoparticles failed to permit stable loading and intracellular delivery of cGAMP for immune response. The nano-STING agonist also mitigated the immunosuppressive tumor microenvironment (TME) by reducing regulatory T cells and polarizing M2 macrophages to the M1 phenotype, thereby creating an immune-supportive TME to enhance adaptive immune responses. The combination of CPGP and immune checkpoint blockers showed synergistic effect, further enhancing the inhibition effect on tumor growth. This double-layer PEI modified CPGP may offer a generalizable platform for other natural dinucleotide STING agonists to overcome the cascade delivery barriers, augmenting immune activation for tumor immunotherapy.
- Immunotherapy,
- Covalent organic polymers,
- Delivery,
- STING agonists,
- Nanoparticle
1. [1]
  K.M. Garland, T.L. Sheehy, J.T. Wilson, Chem. Rev. 122 (2022) 5977–6039. doi: 10.1021/acs.chemrev.1c00750
2. [2]
  M.J. Du, Z.J.J. Chen, Science 361 (2018) 704–709. doi: 10.1126/science.aat1022
3. [3]
  D. Shae, K.W. Becker, P. Christov, et al., Nat. Nanotechnol. 14 (2019) 269–278. doi: 10.1038/s41565-018-0342-5
4. [4]
  S.X. Li, M. Luo, Z.H. Wang, et al., Nat. Biomed. Eng. 5 (2021) 455–466. doi: 10.1038/s41551-020-00675-9
5. [5]
  J. Miller, M. Luo, H. Wang, et al., Cancer Res. 80 (2020) 4577. doi: 10.1158/1538-7445.am2020-4577
6. [6]
  A.F.U.H. Saeed, X.L. Ruan, H.X. Guan, et al., Adv. Sci. 7 (2020) 1902599. doi: 10.1002/advs.201902599
7. [7]
  S.R. Zhou, F.R. Cheng, Y. Zhang, et al., Acc. Chem. Res. 56 (2023) 2933–2943. doi: 10.1021/acs.accounts.3c00394
8. [8]
  M. Petrovic, G. Borchard, O. Jordan, J. Control. Release 339 (2021) 235–247. doi: 10.1016/j.jconrel.2021.09.033
9. [9]
  O. Demaria, E. Vivier, M. Vetizou, et al., J. Immunother. Cancer 9 (2021) A892. doi: 10.1136/jitc-2021-sitc2021.851
10. [10]
  S.S. Gou, W.W. Liu, S. Wang, et al., Nano Lett. 21 (2021) 9939–9950. doi: 10.1021/acs.nanolett.1c03243
11. [11]
  J. Tan, M.F. Wang, B.B. Ding, et al., Coord. Chem. Rev. 493 (2023) 215316. doi: 10.1016/j.ccr.2023.215316
12. [12]
  Z.Y. Wang, Q. Chen, H.M. Zhu, et al., Chin. Chem. Lett. 32 (2021) 1888–1892. doi: 10.1016/j.cclet.2021.01.036
13. [13]
  C.Y. Li, Y.F. Zhang, Y.L. Wan, et al., Chin. Chem. Lett. 32 (2021) 1615–1625. doi: 10.1016/j.cclet.2021.01.001
14. [14]
  X.Q. Sun, Y. Zhang, J.Q. Li, K.S. Park, et al., Nat. Nanotechnol. 16 (2021) 1260–1270. doi: 10.1038/s41565-021-00962-9
15. [15]
  S. Van Herck, B. Feng, L. Tang, Adv. Drug Deliv. Rev. 179 (2021) 114020. doi: 10.1016/j.addr.2021.114020
16. [16]
  Y. Zhang, T.T. Shen, S.R. Zhou, et al., Adv. Ther. 3 (2020) 202000083.
17. [17]
  Y. Liu, W.N. Crowe, L.L. Wang, et al., Nat. Commun. 10 (2019) 5108. doi: 10.7150/jca.33450
18. [18]
  P. Bao, Z.T. Zheng, J.J. Ye, et al., Nano Lett. 22 (2022) 2217–2227. doi: 10.1021/acs.nanolett.1c03996
19. [19]
  P.A. Bielecki, M.E. Lorkowski, W.M. Becicka, et al., Nanoscale Horiz. 6 (2021) 156–167. doi: 10.1039/d0nh00446d
20. [20]
  Y.P. Chen, L. Xu, T.W. Tang, et al., ACS Appl. Mater. Interfaces 12 (2020) 56741–56752. doi: 10.1021/acsami.0c16728
21. [21]
  T. Su, F.R. Cheng, J.L. Qi, et al., Adv. Sci. 9 (2022) 2201895. doi: 10.1002/advs.202201895
22. [22]
  G. Redelman-Sidi, A. Binyamin, I. Gaeta, et al., Cancer Res. 78 (2018) 4658–4670. doi: 10.1158/0008-5472.can-17-3199
23. [23]
  K. Saito-Diaz, H. Benchabane, A. Tiwari, et al., Dev. Cell 44 (2018) 566–581. doi: 10.1016/j.devcel.2018.02.013
24. [24]
  D. Liu, S. Liang, K.S. Ma, et al., Adv. Mater. 36 (2024) 2304845. doi: 10.1002/adma.202304845
25. [25]
  F.M. Chen, T.L. Li, H.J. Zhang, et al., Adv. Mater. 35 (2023) 2304845.
26. [26]
  Y.Y. Hu, L. Lin, Z.P. Guo, et al., Chin. Chem. Lett. 32 (2021) 1770–1774. doi: 10.1016/j.cclet.2020.12.055
27. [27]
  Yu, J., He, S.S., Zhang, C., Xu, et al., Angew. Chem. Int. Ed. 135 (2023) 2307272.
28. [28]
  F.H. Wang, H. Su, Z.Y. Wang, et al., ACS Nano 17 (2023) 10651–10664. doi: 10.1021/acsnano.3c01748
29. [29]
  S. Liang, J.J. Yao, D. Liu, et al., Adv. Mater. 35 (2023) 2211130. doi: 10.1002/adma.202211130
30. [30]
  X.J. Yu, H.T. Ma, G.Y. Xu, et al., Chin. Chem. Lett. 33 (2022) 4169–4174. doi: 10.1016/j.cclet.2022.02.049
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2. [2]
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5. [5]
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6. [6]
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7. [7]
  Junjie Wang , Yan Wang , Zhengdong Li , Changqiang Xie , Musammir Khan , Xingzhou Peng , Fabiao Yu . Triphenylamine-AIEgens photoactive materials for cancer theranostics. Chinese Chemical Letters, 2024, 35(6): 108934-. doi: 10.1016/j.cclet.2023.108934
8. [8]
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9. [9]
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10. [10]
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11. [11]
  Zijian Jiang , Yuang Liu , Yijian Zong , Yong Fan , Wanchun Zhu , Yupeng Guo . Preparation of Nano Zinc Oxide by Microemulsion Method and Study on Its Photocatalytic Activity. University Chemistry, 2024, 39(5): 266-273. doi: 10.3866/PKU.DXHX202311101
12. [12]
  Shuyu Liu , Xiaomin Sun , Bohan Song , Gaofeng Zeng , Bingbing Du , Chongshen Guo , Cong Wang , Lei Wang . Design and Fabrication of Phospholipid-Vesicle-based Artificial Cells towards Biomedical Applications. University Chemistry, 2024, 39(11): 182-188. doi: 10.12461/PKU.DXHX202404113
13. [13]
  Makhloufi Zoulikha , Zhongjian Chen , Jun Wu , Wei He . Approved delivery strategies for biopharmaceuticals. Chinese Chemical Letters, 2025, 36(2): 110225-. doi: 10.1016/j.cclet.2024.110225
14. [14]
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15. [15]
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16. [16]
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17. [17]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
18. [18]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
19. [19]
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20. [20]
  Shenglan Zhou , Haijian Li , Hongyi Gao , Ang Li , Tian Li , Shanshan Cheng , Jingjing Wang , Jitti Kasemchainan , Jianhua Yi , Fengqi Zhao , Wengang Qu . Recent advances in metal-loaded MOFs photocatalysts: From single atom, cluster to nanoparticle. Chinese Chemical Letters, 2025, 36(1): 110142-. doi: 10.1016/j.cclet.2024.110142

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