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, Min Zheng,
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.
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.
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.
4. [4]
  A. Brandenburg, A. Heine, P. Brossart, Trends Cancer 10 (2024) 749, https://doi.org/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.
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.
7. [7]
  H. Liu, Z. Xie, M. Zheng, ACS Appl. Mater. Interfaces 14 (2022) 39858, https://doi.org/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.
9. [9]
  C. Sun, S. Li, J. Ding, Adv. Healthcare Mater. 13 (2024) e2400864, https://doi.org/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.
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.
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.
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.
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.
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.
16. [16]
  Y. Huang, J. Zou, J. Huo, M. Zhang, Y. Yang, Adv. Mater. 36 (2024) e2407914, https://doi.org/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.
18. [18]
  S. Wu, F. Wu, X. Chen, Adv. Mater. 34 (2022) e2109210, https://doi.org/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.
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.
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.
22. [22]
  S. Lu, B. Yang, SmartMat 3 (2022) 207, https://doi.org/10.1002/smm2.1132.
23. [23]
  H. Liu, Z. Xie, M. Zheng, Small 19 (2023) e2206683, https://doi.org/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.
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.
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.
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.
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.
29. [29]
  M. Gao, S. Sun, H. Lin, C. Yang, Chin. Chem. Lett. (2025) 111055, https://doi.org/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.
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.
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.
33. [33]
  M. Li, Z. Xie, M. Zheng, Biosens. Bioelectron. 263 (2024) 116576, https://doi.org/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.
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.
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.
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.
38. [38]
  Y. Li, J. Yang, S. Shen, J. Ding, Nano Today 64 (2025) e102805, https://doi.org/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.
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.
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.
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.
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.
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.
45. [45]
  Y. Guo, P. Hu, J. Shi, J. Am. Chem. Soc. 146 (2024) 10217, https://doi.org/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.
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.
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.
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.
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.
51. [51]
  X. Li, F. Wu, Biosens. Bioelectron. 274 (2025) e117130, https://doi.org/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.
1. [1]
  Tiejin Chen , Xiaokuang Xue , Jian Li , Minhui Cui , Yongliang Hao , Mianqi Xue , Haihua Xiao , Jiechao Ge , Pengfei Wang . Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy. Acta Physico-Chimica Sinica, 2025, 41(10): 100113-0. doi: 10.1016/j.actphy.2025.100113
2. [2]
  Xue Wu , Yupeng Liu , Bingzhe Wang , Lingyun Li , Zhenjian Li , Qingcheng Wang , Quansheng Cheng , Guichuan Xing , Songnan Qu . Rationally assembling different surface functionalized carbon dots for enhanced near-infrared tumor photothermal therapy. Acta Physico-Chimica Sinica, 2025, 41(9): 100109-0. doi: 10.1016/j.actphy.2025.100109
3. [3]
  Wenli FENG , Lu ZHAO , Yunfeng BAI , Feng FENG . Research progress on ultralong room temperature phosphorescent carbon dots. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 833-846. doi: 10.11862/CJIC.20240308
4. [4]
  Yu Liu , Pengfei Li , Yize Liu , Zaicheng Sun . Recent advances in carbon dots as a single photocatalyst. Acta Physico-Chimica Sinica, 2026, 42(2): 100167-0. doi: 10.1016/j.actphy.2025.100167
5. [5]
  Renyi Shao , Khurram Abbas , Vladimir Yu. Osipov , Haimei Zhu , Yuan Li , Usama , Hong Bi . Red-emitting carbon dots prepared from Epipremnum Aureum leaves extract for biological imaging. Acta Physico-Chimica Sinica, 2026, 42(2): 100134-0. doi: 10.1016/j.actphy.2025.100134
6. [6]
  Ting Li , Xiao Zeng , Yuzhuo Yang , Xinyi Wen , Shurong Ding , Linlin Shi , Yongqiang Zhang , Siyu Lu . Towards practical circularly polarized luminescence: carbon dots-based circularly polarized lasers. Acta Physico-Chimica Sinica, 2026, 42(4): 100191-0. doi: 10.1016/j.actphy.2025.100191
7. [7]
  Qianli Ma , Tianbing Song , Tianle He , Xirong Zhang , Huanming Xiong . Sulfur-doped carbon dots: a novel bifunctional electrolyte additive for high-performance aqueous zinc-ion batteries. Acta Physico-Chimica Sinica, 2025, 41(9): 100106-0. doi: 10.1016/j.actphy.2025.100106
8. [8]
  Zihan Cheng , Kai Jiang , Jun Jiang , Henggang Wang , Hengwei Lin . Achieving thermal-stimulus-responsive dynamic afterglow from carbon dots by singlet-triplet energy gap engineering through covalent fixation. Acta Physico-Chimica Sinica, 2026, 42(2): 100169-0. doi: 10.1016/j.actphy.2025.100169
9. [9]
  Chunyuan Kang , Xiaoyu Li , Fan Yang , Bai Yang . Ionic-bond crosslinked carbonized polymer dots for tunable and enhanced room temperature phosphorescence. Acta Physico-Chimica Sinica, 2026, 42(1): 100156-0. doi: 10.1016/j.actphy.2025.100156
10. [10]
  Yinghao Zhang , Huaxin Liu , Hanrui Ding , Zhi Zheng , Wentao Deng , Guoqiang Zou , Laiqiang Xu , Hongshuai Hou , Xiaobo Ji . The application of carbon dots in electrolytes of advanced batteries. Acta Physico-Chimica Sinica, 2026, 42(3): 100170-0. doi: 10.1016/j.actphy.2025.100170
11. [11]
  Tingting XU , Wenjing ZHANG , Yongbo SONG . Research advances of atomic precision coinage metal nanoclusters in tumor therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2275-2285. doi: 10.11862/CJIC.20240229
12. [12]
  Jiahui CHEN , Tingting ZHENG , Xiuyun ZHANG , Wei LÜ . Research progress of near-infrared absorption inorganic nanomaterials in photothermal and photodynamic therapy of tumors. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2396-2414. doi: 10.11862/CJIC.20240106
13. [13]
  Fa Wang , Yu Chen , Hui Chao . Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy. University Chemistry, 2025, 40(7): 200-212. doi: 10.12461/PKU.DXHX202410024
14. [14]
  Yan Long , Wenbo Zhao , Qing Cao , Xiangyu Li , Fukui Li , Yanwei Hu , Shiyu Song , Kaikai Liu . Phosphorescent carbon nanodot inks for scalable and high-resolution invisible printing. Acta Physico-Chimica Sinica, 2026, 42(3): 100198-0. doi: 10.1016/j.actphy.2025.100198
15. [15]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . Highly Efficient, Targeted, and Traceable Perovskite Nanocrystals for Photoelectrocatalytic Oncotherapy. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-0. doi: 10.1016/j.actphy.2024.100042
16. [16]
  Tong WANG , Qinyue ZHONG , Qiong HUANG , Weimin GUO , Xinmei LIU . Mn-doped carbon quantum dots/Fe-doped ZnO flower-like microspheres heterojunction: Construction and photocatalytic performance. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1589-1600. doi: 10.11862/CJIC.20250011
17. [17]
  Shuting Zhuang , Lida Zhao . Teaching through Research: A Comprehensive Experiment on Carbon Quantum Dots from Microplastic Waste. University Chemistry, 2025, 40(10): 217-224. doi: 10.12461/PKU.DXHX202412010
18. [18]
  Yue WANG , Zhizhi GU , Jingyi DONG , Jie ZHU , Cunguang LIU , Guohan LI , Meichen LU , Jian HAN , Shengnan CAO , Wei WANG . Effects of kelp-derived carbon dots on embryonic development of zebrafish. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1209-1217. doi: 10.11862/CJIC.20230423
19. [19]
  Qi WANG , Ying CHENG , Yuyan WANG , Yibing XIAO , Haozhe LU , Yansong ZHANG , Shengling LI , Jiazi TANTAI , Na SUN , Lifeng DING , Jinqin GUO , Peng JIN . "Shining dot" in vinegar—Extraction of carbon quantum dots and the fluorescence properties analysis. Chinese Journal of Inorganic Chemistry, 2026, 42(1): 87-96. doi: 10.11862/CJIC.20250127
20. [20]
  Siwei Hou , Yaxin Niu , Guanglu Zhang , Yanmei Yang , Xu Wang , Zhenzhen Chen . Application of Solid-Phase Microextraction and Mass Spectrometry in Environmental Detection. University Chemistry, 2026, 41(3): 297-306. doi: 10.12461/PKU.DXHX202504078

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(9)
HTML views(0)

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