Citation: Qingwen Xu, Zhigang Xie, Min Zheng. Construction of pH-responsive Lycium barbarum-derived carbon dots nanovaccines for enhanced anti-tumor immunotherapy[J]. Acta Physico-Chimica Sinica, ;2026, 42(6): 100203. doi: 10.1016/j.actphy.2025.100203 shu

Construction of pH-responsive Lycium barbarum-derived carbon dots nanovaccines for enhanced anti-tumor immunotherapy

Qingwen Xu ¹ ,
Zhigang Xie ^2,, ,
Min Zheng ^1,,

1.
College of Chemistry and Life Sciences, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, Jilin Province, China
2.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin Province, China

Corresponding author: Zhigang Xie, xiez@ciac.ac.cn Min Zheng, zhengm@ciac.ac.cn
Received Date: 1 September 2025
Revised Date: 19 October 2025
Accepted Date: 19 October 2025

Immunotherapy has become a key focus in cancer treatment, and cancer nanovaccines have made significant progress as a representative approach in this field. However, some issues such as low immunogenicity, inefficient antigen delivery, and poor immune responses have limited the advancement of immunotherapy. To address these limitations, this study developed a pH-responsive nanovaccine (Lyc-OVA) based on Lycium barbarum-derived carbon dots (Lyc-CDs) synthesized via a green hydrothermal method. Owing to retained Lycium barbarum polysaccharides (LBP, 18.43% total sugar content), Lyc-CDs demonstrated superior loading efficiency (48.40%) and pH-responsive release (80% OVA released within 24 h at pH 5.4) of OVA. Molecular docking simulations identified hydrogen bonding and π-cation interactions between LBP monosaccharides (rhamnose/galactose) and OVA. Lyc-OVA promoted dendritic cell maturation (32.87% CD80⁺CD86⁺ cells, comparable to LPS) and cytokine secretion (TNF-α: 13.10 pg mL⁻¹; IFN-γ: 17.78 pg mL⁻¹; IL-6: 3.74 pg mL⁻¹). In a bilateral B16-OVA melanoma model, Lyc-OVA suppressed primary/distal tumor growth (80.36%/82.16% inhibition rates) by activating CD4⁺CD8⁺T cells, reducing immunosuppressive Treg/MDSC populations, and reshaping the tumor immune microenvironment. This work highlights the multifunctional role of natural polysaccharides in nanovaccine and provides an effective strategy for tumor immunotherapy.
- Lycium barbarum,
- Carbon dots,
- Nanovaccines,
- Tumor microenvironment,
- Tumor immunotherapy
1. [1]
  H. Liu, T. Zhang, M. Zheng, Z. Xie, J. Colloid Interface Sci. 673 (2024) 594, https://doi.org/10.1016/j.jcis.2024.06.101. doi: 10.1016/j.jcis.2024.06.101
2. [2]
  P. Guasp, C. Reiche, Z. Sethna, V. Balachandran, Cancer Cell 42 (2024) 1163, https://doi.org/10.1016/j.ccell.2024.05.005. doi: 10.1016/j.ccell.2024.05.005
3. [3]
  W. Zhang, X. Shi, S. Huang, Q. Yu, Z. Wu, W. Xie, B. Li, Y. Xu, Z. Gao, G. Li, et al., Cancer Immunol. Immunother. 73 (2024) 245, https://doi.org/10.1007/s00262-024-03830-2. doi: 10.1007/s00262-024-03830-2
4. [4]
  A. Brandenburg, A. Heine, P. Brossart, Trends Cancer 10 (2024) 749, https://doi.org/10.1016/j.trecan.2024.06.003. doi: 10.1016/j.trecan.2024.06.003
5. [5]
  X. Zhu, T. Wang, H. Jia, F. Wu, Adv. Funct. Mater. 32 (2022) e2207181, https://doi.org/10.1002/adfm.202207181. doi: 10.1002/adfm.202207181
6. [6]
  G. Jin, H. Liu, Z. Mei, Q. Jin, S. Ma, L. Wang, Y. Su, L. Lv, Z. Wang, H. Zhou, et al., Bioact. Mater. 45 (2025) 102, https://doi.org/10.1016/j.bioactmat.2024.11.008. doi: 10.1016/j.bioactmat.2024.11.008
7. [7]
  H. Liu, Z. Xie, M. Zheng, ACS Appl. Mater. Interfaces 14 (2022) 39858, https://doi.org/10.1021/acsami.2c11596. doi: 10.1021/acsami.2c11596
8. [8]
  Z. Cui, C. Shi, R. An, Y. Tang, Y. Li, X. Cao, X. Jiang, C. Liu, M. Xiao, L. Xu, ACS Nano 19 (2025) 2099, https://doi.org/10.1021/acsnano.4c08898. doi: 10.1021/acsnano.4c08898
9. [9]
  C. Sun, S. Li, J. Ding, Adv. Healthcare Mater. 13 (2024) e2400864, https://doi.org/10.1002/adhm.202400864. doi: 10.1002/adhm.202400864
10. [10]
  C. Zhang, G. Shi, J. Zhang, H. Song, J. Niu, S. Shi, P. Huang, Y. Wang, W. Wang, C. Li, et al., J. Control. Release 256 (2017) 170, https://doi.org/10.1016/j.jconrel.2017.04.020. doi: 10.1016/j.jconrel.2017.04.020
11. [11]
  W. Zhang, W. Ma, J. Zhang, X. Song, W. Sun, Y. Fan, Int. J. Biol. Macromol. 105 (2017) 852, https://doi.org/10.1016/j.ijbiomac.2017.07.108. doi: 10.1016/j.ijbiomac.2017.07.108
12. [12]
  L. Zhou, L. Zhao, M. Wang, X. Qi, X. Zhang, Q. Song, D. Xue, M. Mao, Z. Zhang, J. Shi, et al., Adv. Sci. 11 (2024) e2402199, https://doi.org/10.1002/advs.202402199. doi: 10.1002/advs.202402199
13. [13]
  J. Zhou, K. Tison, H. Zhou, L. Bai, R. Acharyya, D. McEachern, H. Metwally, Y. Wang, M. Pitter, J. Choi, et al., Nature 643 (2025) 519, https://doi.org/10.1038/s41586-025-09000-3. doi: 10.1038/s41586-025-09000-3
14. [14]
  H. Fang, Y. Wu, L. Chen, Z. Cao, Z. Deng, R. Zhao, L. Zhang, Y. Yang, Z. Liu, Q. Chen, ACS Nano 17 (2023) 4748, https://doi.org/10.1021/acsnano.2c11159. doi: 10.1021/acsnano.2c11159
15. [15]
  D. Han, X. Liao, Q. Huang, L. Qi, C. Xu, X. Ren, X. He, T. Guo, Y. Huang, X. Pang, et al., ACS Nano 19 (2025) 20808, https://doi.org/10.1021/acsnano.5c03116. doi: 10.1021/acsnano.5c03116
16. [16]
  Y. Huang, J. Zou, J. Huo, M. Zhang, Y. Yang, Adv. Mater. 36 (2024) e2407914, https://doi.org/10.1002/adma.202407914. doi: 10.1002/adma.202407914
17. [17]
  L. Li, J. Wu, X. Wu, Z. Li, X. Zhang, Z. Yan, Y. Liang, C. Huang, S. Qu, Adv. Mater. 37 (2025) e2420068, https://doi.org/10.1002/adma.202420068. doi: 10.1002/adma.202420068
18. [18]
  S. Wu, F. Wu, X. Chen, Adv. Mater. 34 (2022) e2109210, https://doi.org/10.1002/adma.202109210. doi: 10.1002/adma.202109210
19. [19]
  J. Zhang, J. Liu, H. Zhang, B. Liu, L. Li, Y. Li, J. Pei, Q. Lin, Q. Chen, J. Lin, Mater. Today Bio 31 (2025) e101559, https://doi.org/10.1016/j.mtbio.2025.101559. doi: 10.1016/j.mtbio.2025.101559
20. [20]
  J. Sun, Z. Huangfu, J. Yang, G. Wang, K. Hu, M. Gao, Z. Zhong, Adv. Drug Deliv. Rev. 190 (2022) e114538, https://doi.org/10.1016/j.addr.2022.114538. doi: 10.1016/j.addr.2022.114538
21. [21]
  M. Chen, J. Jiang, H. Chen, R. Wu, W. Xie, S. Dai, W. Zheng, G. Tan, F. Huang, J. Immunother. Cancer 13 (2025) e010150, https://doi.org/10.1136/jitc-2024-010150. doi: 10.1136/jitc-2024-010150
22. [22]
  S. Lu, B. Yang, SmartMat 3 (2022) 207, https://doi.org/10.1002/smm2.1132. doi: 10.1002/smm2.1132
23. [23]
  H. Liu, Z. Xie, M. Zheng, Small 19 (2023) e2206683, https://doi.org/10.1002/smll.202206683. doi: 10.1002/smll.202206683
24. [24]
  J. Liu, R. Li, B. Yang, ACS Cent. Sci. 6 (2020) 2179, https://doi.org/10.1021/acscentsci.0c01306. doi: 10.1021/acscentsci.0c01306
25. [25]
  H. Feng, Y. Hong, Q. Li, S. Qu, Chem. Eng. J. 502 (2024) 157991, https://doi.org/10.1016/j.cej.2024.157991. doi: 10.1016/j.cej.2024.157991
26. [26]
  Y. Zhang, J. Wang, L. Wang, R. Fu, L. Sui, H. Song, Y. Hu, S. Lu, Adv. Mater. 35 (2023) e2302536, https://doi.org/10.1002/adma.202302536. doi: 10.1002/adma.202302536
27. [27]
  F. Shan, J. Zhang, C. Liao, Y. Liu, X. Li, H. Mi, W. Wang, S. Jiang, M. Li, Y. Liu, et al., ACS Nano 19 (2025) 20205, https://doi.org/10.1021/acsnano.5c05934. doi: 10.1021/acsnano.5c05934
28. [28]
  Y. Hu, O. Seivert, Y. Tang, H. Karahan, A. Bianco, Angew. Chem. Int. Ed. 63 (2024) 202412341, https://doi.org/10.1002/anie.202412341. doi: 10.1002/anie.202412341
29. [29]
  M. Gao, S. Sun, H. Lin, C. Yang, Chin. Chem. Lett. (2025) 111055, https://doi.org/10.1016/j.cclet.2025.111055. doi: 10.1016/j.cclet.2025.111055
30. [30]
  Y. Xu, B. Wang, M. Zhang, J. Zhang, Y. Li, P. Jia, H. Zhang, L. Duan, Y. Li, Y. Li, et al., Adv. Mater. 34 (2022) e2200905, https://doi.org/10.1002/adma.202200905. doi: 10.1002/adma.202200905
31. [31]
  J. Li, W. Fu, X. Zhang, Q. Zhang, D. Ma, Y. Wang, W. Qian, D. Zhu, Carbon 208 (2023) 208, https://doi.org/10.1016/j.carbon.2023.03.039. doi: 10.1016/j.carbon.2023.03.039
32. [32]
  P. Liang, T. Bi, Y. Zhou, C. Wang, Y. Ma, H. Xu, H. Shen, W. Ren, S. Yang, Small 19 (2023) e2303498, https://doi.org/10.1002/smll.202303498. doi: 10.1002/smll.202303498
33. [33]
  M. Li, Z. Xie, M. Zheng, Biosens. Bioelectron. 263 (2024) 116576, https://doi.org/10.1016/j.bios.2024.116576. doi: 10.1016/j.bios.2024.116576
34. [34]
  Z. Li, R. Zhao, Q. Pei, Z. Xie, M. Zheng, Adv. Sci. (2025) 03883, https://doi.org/10.1002/advs.202503883. doi: 10.1002/advs.202503883
35. [35]
  L. Yang, F. Dai, H. Tang, M. Li, Y. An, Y. Tan, R. Liu, X. Tan, W. Zhang, S. Rizvi, et al., Chem. Eng. J. 513 (2025) e162637, https://doi.org/10.1016/j.cej.2025.162637. doi: 10.1016/j.cej.2025.162637
36. [36]
  G. Zhang, C. Kang, H. Chen, W. Tian, H. Liu, Chem. Eng. J. 508 (2025) e160594, https://doi.org/10.1016/j.cej.2025.160594. doi: 10.1016/j.cej.2025.160594
37. [37]
  M. Fang, B. Wang, X. Qu, S. Li, J. Huang, J. Li, S. Lu, N. Zhou, Chin. Chem. Lett. 35 (2024) 64, https://doi.org/10.1016/j.cclet.2023.108423. doi: 10.1016/j.cclet.2023.108423
38. [38]
  Y. Li, J. Yang, S. Shen, J. Ding, Nano Today 64 (2025) e102805, https://doi.org/10.1016/j.nantod.2025.102805. doi: 10.1016/j.nantod.2025.102805
39. [39]
  L. Gu, J. Zhang, G. Yang, Y. Tang, X. Zhang, X. Huang, W. Zhai, E. Fodjo, C. Kong, Food Chem. 376 (2022) 131898, https://doi.org/10.1016/j.foodchem.2021.131898. doi: 10.1016/j.foodchem.2021.131898
40. [40]
  Z. Guo, Z. Wang, Y. Liu, H. Wu, Q. Zhang, J. Han, J. Liu, C. Zhang, ACS Appl. Mater. Interfaces 15 (2023) 20726, https://doi.org/10.1021/acsami.3c01322. doi: 10.1021/acsami.3c01322
41. [41]
  D. Wu, H. Guo, S. Lin, S. Lam, L. Zhao, D. Lin, W. Qin, Trends Food Sci. Technol. 79 (2018) 171, https://doi.org/10.1016/j.tifs.2018.07.016. doi: 10.1016/j.tifs.2018.07.016
42. [42]
  L. Sun, Y. Liu, Q. Sun, G. Wang, B. Du, B. Liu, T. Gao, P. Zhao, Y. Yang, R. Rong, et al., Carbohydr. Polym. 357 (2025) 123416, https://doi.org/10.1016/j.carbpol.2025.123416. doi: 10.1016/j.carbpol.2025.123416
43. [43]
  Y. Liu, L. Zhang, H. Cai, X. Qu, J. Chang, G. Waterhouse, S. Lu, Sci. Bull. 69 (2024) 3127, https://doi.org/10.1016/j.scib.2024.08.011. doi: 10.1016/j.scib.2024.08.011
44. [44]
  L. Sushytskyi, A. Synytsya, P. Lukac, L. Rajsiglová, P. Capek, R. Pohl, R. Bleha, L. Vannucci, D. Smrz, J. Copíková, et al., Carbohydr. Polym. 353 (2025) 123242, https://doi.org/10.1016/j.carbpol.2025.123242. doi: 10.1016/j.carbpol.2025.123242
45. [45]
  Y. Guo, P. Hu, J. Shi, J. Am. Chem. Soc. 146 (2024) 10217, https://doi.org/10.1021/jacs.3c14005. doi: 10.1021/jacs.3c14005
46. [46]
  X. Qiu, Y. Qu, B. Guo, H. Zheng, F. Meng, Z. Zhong, J. Control. Release 341 (2022) 498, https://doi.org/10.1016/j.jconrel.2021.12.002. doi: 10.1016/j.jconrel.2021.12.002
47. [47]
  C. Chao, E. Zhang, D. Trinh, E. Udofa, H. Lin, C. Silvers, J. Huo, S. He, J. Zheng, X. Cai, et al., Nat. Commun. 16 (2025) e4578, https://doi.org/10.1038/s41467-025-59840-w. doi: 10.1038/s41467-025-59840-w
48. [48]
  P. Chou, S. Lin, Y. Wu, C. Shen, M. Sheu, H. Ho, J. Control. Release 351 (2022) 970, https://doi.org/10.1016/j.jconrel.2022.10.002. doi: 10.1016/j.jconrel.2022.10.002
49. [49]
  P. Zhang, T. Wang, G. Cui, R. Ye, W. Wan, T. Liu, Y. Zheng, Z. Zhong, Adv. Mater. 36 (2024) e2407189, https://doi.org/10.1002/adma.202407189. doi: 10.1002/adma.202407189
50. [50]
  Z. Guo, T. Huang, X. Lv, R. Yin, P. Wan, G. Li, P. Zhang, C. Xiao, X. Chen, Biomaterials 314 (2025) e122870, https://doi.org/10.1016/j.biomaterials.2024.122870. doi: 10.1016/j.biomaterials.2024.122870
51. [51]
  X. Li, F. Wu, Biosens. Bioelectron. 274 (2025) e117130, https://doi.org/10.1016/j.bios.2025.117130. doi: 10.1016/j.bios.2025.117130
52. [52]
  Y. Jiang, S. Qi, C. Mao, Acta Pharm. Sin. B 15 (2025) 1796, https://doi.org/10.1016/j.apsb.2025.03.006. doi: 10.1016/j.apsb.2025.03.006
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