Citation: Youcheng Hu, Guichan Li, Chunli Qi, Xiaoyan Lin, Xingwang Zhang, Hao Wang. Macrophage membrane-engineered nanovesicles for targeted delivery of emodin in ulcerative colitis via chemotactic homing[J]. Chinese Chemical Letters, ;2026, 37(7): 111727. doi: 10.1016/j.cclet.2025.111727 shu

Macrophage membrane-engineered nanovesicles for targeted delivery of emodin in ulcerative colitis via chemotactic homing

Youcheng Hu ^{a, 1} ,
Guichan Li ^{b, 1} ,
Chunli Qi ^c ,
Xiaoyan Lin ^c ,
Xingwang Zhang ^{b, *,} ,
Hao Wang ^{a, *,}

a.
Department of Anesthesiology and Clinical Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
b.
Department of Pharmaceutics, School of Pharmacy, Jinan University, Guangzhou 511443, China
c.
Institute of Laboratory Animals, Jinan University, Guangzhou 510632, China

zhangxw@jnu.edu.cn

haowang@jnu.edu.cn

Received Date: 23 June 2025
Revised Date: 13 August 2025
Accepted Date: 15 August 2025
Available Online: 16 August 2025

Figures(4)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease featured by dysregulated immune responses and compromised intestinal barrier function. Current therapies often suffer from limited efficacy and systemic side effects due to non-specific drug distribution. Here, we developed macrophage membrane-camouflaged nanovesicles (mcNVs) for targeted delivery of emodin (Emo) to inflamed colon tissues. The biomimetic nanovesicles were fabricated by fusing J774A.1 macrophage membranes with Emo-loaded liposomes, inheriting the parent cells' chemotactic homing capabilities while maintaining excellent drug loading and colloidal stability. Systematic characterization confirmed successful membrane integration, as evidenced by transmission electron microscope (TEM) imaging, particle size, and ζ potential analyses. In vitro studies demonstrated favorable sustained release and enhanced cellular uptake of Emo-loaded mcNVs (Emo-mcNVs) compared to conventional liposomes. In a sodium dextran sulfate (DSS)-induced murine colitis model, Emo-mcNVs exhibited superior colon-targeting capability through chemokine gradient recognition (C-C motif chemokine ligand (CCL)2/3/5), resulting in significantly improved therapeutic outcomes versus free Emo and 5-aminosalicylic acid controls. Treatment with Emo-mcNVs attenuated disease severity (reduced disease activity index (DAI) score), preserved the colon architecture, and decreased pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6). Biodistribution studies using multimodal imaging confirmed specific accumulation in the inflamed colon tissue with minimal systemic exposure. This study presents a novel biohybrid delivery system that leverages the pathophysiology of UC for targeted therapy, offering a promising translational approach for inflammatory bowel diseases.
- Nanovesicles,
- Macrophage,
- Emodin,
- Ulcerative colitis,
- Targeted therapy,
- Chemokine
1. [1]
  V. Jairath, N. Narula, R.C. Ungaro, et al., J. Crohns Colitis 19 (2025) jjaf040. doi: 10.1093/ecco-jcc/jjaf040
2. [2]
  A. Di Rienzo, L. Marinelli, M.P. Dimmito, et al., Pharmaceutics. 16 (2024) 1185. doi: 10.3390/pharmaceutics16091185
3. [3]
  P. Wangchuk, K. Yeshi, A. Loukas, Trends Pharmacol. Sci. 45 (2024) 892–903. doi: 10.1016/j.tips.2024.08.003
4. [4]
  Y. Liang, Y. Li, C. Lee, et al., Mol. Biomed. 5 (2024) 42. doi: 10.54254/2754-1169/123/2024mur0120
5. [5]
  J. Zhao, S. Hao, Y. Chen, et al., Colloids Surf. B: Biointerfaces 236 (2024) 113798. doi: 10.1016/j.colsurfb.2024.113798
6. [6]
  S. Luo, J. He, S. Huang, et al., Phytomedicine 104 (2022) 154106. doi: 10.1016/j.phymed.2022.154106
7. [7]
  Y.Y. Xu, M. Zhu, J. Wu, et al., Chin. Med. 18 (2023) 98. doi: 10.1186/s13020-023-00801-0
8. [8]
  Z. Ai, B. Liu, J. Chen, et al., Int. J. Pharm. X 9 (2025) 100314.
9. [9]
  X. Chen, X. Ling, L. Zhao, et al., ACS Appl. Mater. Interfaces 10 (2018) 33976–33985. doi: 10.1021/acsami.8b11571
10. [10]
  F. Xiong, X. Ling, X. Chen, et al., Nano Lett. 19 (2019) 3256–3266. doi: 10.1021/acs.nanolett.9b00824
11. [11]
  Z. Fang, X. Zhang, H. Huang, et al., Chin. Chem. Lett. 33 (2022) 1693–1704. doi: 10.1016/j.cclet.2021.11.050
12. [12]
  Y. Wang, C. Zhang, S. Han, et al., Chin. Chem. Lett. 35 (2024) 109578. doi: 10.1016/j.cclet.2024.109578
13. [13]
  H.L. Wang, Z. Peng, Y.Q. Li, et al., Inflamm. Res. 73 (2024) 1267–1282. doi: 10.1007/s00011-024-01899-0
14. [14]
  A.J. Burnham, A.I. Toma, D. Shah, et al., Cytotherapy 27 (2025) 338–349. doi: 10.1016/j.jcyt.2024.11.002
15. [15]
  Y. Qian, Z. Yan, T. Ye, et al., Exploration 4 (2024) 20230098. doi: 10.1002/EXP.20230098
16. [16]
  C. Gu, X. Geng, Y. Wu, et al., Small 20 (2024) e2305659. doi: 10.1002/smll.202305659
17. [17]
  A. Zhou, K. Chen, Y. Gao, et al., ACS Nano 17 (2023) 16461–16477. doi: 10.1021/acsnano.3c00227
18. [18]
  M.J. Zhu, S.P. Zhu, Q.B. Liu, et al., Chin. Chem. Lett. 34 (2023) 107482. doi: 10.1016/j.cclet.2022.04.080
19. [19]
  Y.T. Sato, K. Umezaki, S. Sawada, et al., Sci. Rep. 6 (2016) 21933. doi: 10.1038/srep21933
20. [20]
  C.L. Lin, Z.S. Fang, C.Y. Hsu, et al., Acta Biomater. 173 (2024) 325–335. doi: 10.1007/978-3-031-66968-2_32
21. [21]
  D. Hu, Z. Huang, W. Li, et al., Mol. Pharm. 22 (2025) 771–786. doi: 10.1021/acs.molpharmaceut.4c00808
22. [22]
  Y. Ma, H. He, W. Fan, et al., ACS Biomater. Sci. Eng. 3 (2017) 2399–2409. doi: 10.1021/acsbiomaterials.7b00380
23. [23]
  O.J. Hedge, F. Höök, P. Joyce, et al., Langmuir 37 (2021) 10200–10213. doi: 10.1021/acs.langmuir.1c01689
24. [24]
  N. Jan, A. Madni, S. Khan, et al., Bioeng. Transl. Med. 8 (2023) e10441. doi: 10.1002/btm2.10441
25. [25]
  Y. Li, C. Zhu, Int. J. Nanomedicine 12 (2017) 1673–1684. doi: 10.2147/IJN.S125047
26. [26]
  L. Hou, X. Gong, J. Yang, et al., Adv. Mater. 34 (2022) e2200389. doi: 10.1002/adma.202200389
27. [27]
  K. Dong, S.J. Deng, B.Y. He, et al., Drug Des. Devel. Ther. 17 (2023) 191–207. doi: 10.2147/dddt.s390274
28. [28]
  J. Xian, X. Zhong, H. Gu, et al., Pharmaceutics 13 (2021) 2025. doi: 10.3390/pharmaceutics13122025
29. [29]
  S. Luo, X. Deng, Q. Liu, et al., Int. Immunopharmacol. 59 (2018) 269–275. doi: 10.1016/j.intimp.2018.04.010
30. [30]
  Y. Zhang, W. Pu, M. Bousquenaud, et al., Front. Oncol. 10 (2020) 564674.
31. [31]
  D. Yang, T. Ge, J. Zhou, et al., Heliyon 10 (2024) e34932. doi: 10.1016/j.heliyon.2024.e34932
32. [32]
  Y. Li, R. Guo, M. Zhang, et al., Exp. Ther. Med. 19 (2020) 3521–3530. doi: 10.1080/23802359.2020.1827059
33. [33]
  H.I. Tong, W. Kang, P.M. Davy, et al., PLoS One 11 (2016) e0154022. doi: 10.1371/journal.pone.0154022
34. [34]
  W. Yu, B. Li, L. Chen, et al., J. Ethnopharmacol. 328 (2024) 118123. doi: 10.1016/j.jep.2024.118123
35. [35]
  L. Xu, J. Gao, D. Huang, et al., Biochem. Biophys. Res. Commun. 534 (2021) 279–285. doi: 10.1145/3478905.3478960
36. [36]
  D. Yan, Y. Wei, X. Ye, et al., ACS Appl. Mater. Interfaces 17 (2025) 13676–13689. doi: 10.1021/acsami.4c22525
37. [37]
  H. Luo, X. Ji, M. Zhang, et al., Mini Rev. Med. Chem. 24 (2024) 1784–1798. doi: 10.2174/0113895575298364240409064833
38. [38]
  Y. Cai, X. Ji, Y. Zhang, et al., Aggregate 4 (2023) e277. doi: 10.1002/agt2.277
39. [39]
  H. He, C. Liu, J. Ming, et al., Aggregate 3 (2022) e163. doi: 10.1002/agt2.163
40. [40]
  W. Fan, H. Peng, Z. Yu, et al., Acta Pharm. Sin. B 12 (2022) 2479–2493. doi: 10.1016/j.apsb.2021.11.016
41. [41]
  C. Liu, Y. Cai, Z. Zhang, et al., Acta Pharm. Sin. B 14 (2024) 3155–3168. doi: 10.1016/j.apsb.2024.04.002
42. [42]
  Z. Zhang, C. Liu, Y. Lu, et al., J. Nanobiotechnology 22 (2024) 488. doi: 10.2991/978-94-6463-570-6_48
43. [43]
  X. Ji, A. Raza, J. Qi, et al., J. Pharm. Anal. 15 (2025) 101044. doi: 10.1016/j.jpha.2024.101044
44. [44]
  X. Wu, Q. Zhang, L. Peng, et al., J. Mater. Chem. B 12 (2024) 1604–1616. doi: 10.1039/d3tb02312e
45. [45]
  S. Fan, Y. Zhao, Y. Yao, et al., J. Transl. Med. 22 (2024) 878. doi: 10.1186/s12967-024-05662-1
46. [46]
  Z. Zhuo, K. Guo, Y. Luo, et al., Theranostics 14 (2024) 528–546. doi: 10.7150/thno.87739
47. [47]
  C.E. Hughes, R.J.B. Nibbs, FEBS J. 285 (2018) 2944–2971. doi: 10.1111/febs.14466
48. [48]
  K. Wang, Y. Wang, L. Wang, et al., Chin. Chem. Lett. 36 (2025) 109868. doi: 10.1016/j.cclet.2024.109868
49. [49]
  Y. Song, Y. Huang, F. Zhou, et al., Chin. Chem. Lett. 33 (2022) 597–612. doi: 10.1016/j.cclet.2021.08.090
50. [50]
  S. Melgar, M. Drmotova, E. Rehnström, et al., Cytokine 35 (2006) 275–283. doi: 10.1016/j.cyto.2006.09.007
51. [51]
  M. Li, S. Li, H. Zhou, et al., Nat. Commun. 11 (2020) 1126. doi: 10.1038/s41467-020-14963-0
52. [52]
  T. Zhang, P. Liu, W. Shen, et al., Adv. Sci. 12 (2025) e03689. doi: 10.1002/advs.202503689
53. [53]
  Y. Li, Z. Cai, Z. Wang, et al., Chin. Chem. Lett. 36 (2025) 109942. doi: 10.1016/j.cclet.2024.109942
54. [54]
  Y. Yu, T. Li, M. Ou, et al., J. Control. Release 365 (2024) 469–479. doi: 10.1016/j.jconrel.2023.11.051
55. [55]
  Y. Yu, F. Zhang, W. Xiao, et al., ACS Nano 18 (2024) 5915–5929.
1. [1]
  Shuang Li , Penghui Yuan , Xinyi Zhang , Meiru Liu , Dezhi Yang , Linglei Kong , Li Zhang , Yang Lu , Guanhua Du . Revolutionizing sepsis therapy: Machine learning-driven co-crystallization reveals emodin's therapeutic potential. Chinese Chemical Letters, 2026, 37(2): 111289-. doi: 10.1016/j.cclet.2025.111289
2. [2]
  Jia-Lun Duan , Xin-Lan Zhang , Li-Qiang Zhao , Ya-Nan Liu , An-Ni Yao , Nian-Guang Li , Jin-Ao Duan , Chun-Jie Bao . Macrophage membrane-camouflaged nanoparticles for targeted drug delivery. Chinese Chemical Letters, 2026, 37(7): 111610-. doi: 10.1016/j.cclet.2025.111610
3. [3]
  Yu Yan , Jiawei Song , Dongdong Liu , Zihan Liu , Jialing Cheng , Zhiyang Chen , Yanfang Yang , Weizhe Jiang , Hongliang Wang , Jun Ye , Yuling Liu . Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis. Chinese Chemical Letters, 2024, 35(6): 109736-. doi: 10.1016/j.cclet.2024.109736
4. [4]
  Jia Deng , Jianbin Shi , Dan Li , Xue Jiao , Jinrui Liu , Haowen Tian , Na Liu , Cong Luo , Ken-ichiro Kamei , Chutong Tian . Cancer-targeting drug conjugates drives a new era in precise cancer treatment. Chinese Chemical Letters, 2026, 37(2): 110960-. doi: 10.1016/j.cclet.2025.110960
5. [5]
  Si Ha , Jiacheng Zhu , Hua Xiang , Guoshun Luo . Hydrophobic tag tethering degrader as a promising paradigm of protein degradation: Past, present and future perspectives. Chinese Chemical Letters, 2024, 35(8): 109192-. doi: 10.1016/j.cclet.2023.109192
6. [6]
  Linzhou Yin , Xiaowen Jiang , Miao Wang , Yiren Yang , Zhonggui He , Jin Sun , Huiyuan Gao , Mengchi Sun . Phytoconstituent-derived nano-medicines/vesicles providing a promising dawn for inflammatory bowel disease. Chinese Chemical Letters, 2025, 36(6): 110224-. doi: 10.1016/j.cclet.2024.110224
7. [7]
  Xinyi Wang , Iek Man Lei , Bei Li , Yunlu Dai . Progress in extracellular vesicle@STING towards immune regulation. Chinese Chemical Letters, 2026, 37(2): 110990-. doi: 10.1016/j.cclet.2025.110990
8. [8]
  Weijian Zhang , Xianyu Deng , Liying Wang , Jian Wang , Xiuting Guo , Lianggui Huang , Xinyi Wang , Jun Wu , Linjia Jiang . Poly(ferulic acid) nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages. Chinese Chemical Letters, 2024, 35(9): 109422-. doi: 10.1016/j.cclet.2023.109422
9. [9]
  Xiongbo Song , Jinwen Xiao , Juan Wu , Li Sun , Long Chen . Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/AKT/HIF-1α pathway. Chinese Chemical Letters, 2025, 36(1): 109844-. doi: 10.1016/j.cclet.2024.109844
10. [10]
  Zhiqiang Cui , Dongxiang Zhang , Yanru Huang , Chunyu Shao , Yiming Zhang , Changliang Sun , Xin-Dong Jiang , Xiaohong Sun , Qinghuan Xiao . Novel 1-phenylethyl-containing aza-BDOIPY for phototherapy and simultaneous monitoring of tumor immune microenvironment reprogramming. Chinese Chemical Letters, 2025, 36(7): 110460-. doi: 10.1016/j.cclet.2024.110460
11. [11]
  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
12. [12]
  Yangyang Zhang , Lu Qiu , Houying Li , Wenli Cai , Ergang Liu , Hongtao Zhang , Bahtiyor Muhitdinov , Jianming Liang , Yongzhuo Huang . Biomimetically engineered plant-derived exosomes-like nanovesicles for rheumatoid arthritis therapy. Chinese Chemical Letters, 2025, 36(9): 110658-. doi: 10.1016/j.cclet.2024.110658
13. [13]
  Kai Wang , Yun Wang , Lihang Wang , Zhuhai Li , Xi Yu , Xuanhe You , Diwei Wu , Yueming Song , Jiancheng Zeng , Zongke Zhou , Shishu Huang , Yunfeng Lin . Therapeutic siRNA targeting CC chemokine receptor 2 loaded with tetrahedral framework nucleic acid alleviates neuropathic pain by regulating microglial polarization. Chinese Chemical Letters, 2025, 36(3): 109868-. doi: 10.1016/j.cclet.2024.109868
14. [14]
  Chao Zhang , Ai-Feng Liu , Shihui Li , Fang-Yuan Chen , Jun-Tao Zhang , Fang-Xing Zeng , Hui-Chuan Feng , Ping Wang , Wen-Chao Geng , Chuan-Rui Ma , Dong-Sheng Guo . A supramolecular formulation of icariin@sulfonatoazocalixarene for hypoxia-targeted osteoarthritis therapy. Chinese Chemical Letters, 2025, 36(1): 109752-. doi: 10.1016/j.cclet.2024.109752
15. [15]
  Wenhao Wang , Siyuan Peng , Zhengwei Huang , Xin Pan . Tuning amino/hydroxyl ratios of nanovesicles to manipulate protein corona-mediated in vivo fate. Chinese Chemical Letters, 2024, 35(11): 110134-. doi: 10.1016/j.cclet.2024.110134
16. [16]
  Feifei Wang , Hang Yao , Xinyue Wu , Yijian Tang , Yang Bai , Hui Chong , Huan Pang . Metal–organic framework and its composites modulate macrophage polarization in the treatment of inflammatory diseases. Chinese Chemical Letters, 2024, 35(5): 108821-. doi: 10.1016/j.cclet.2023.108821
17. [17]
  Chuyu Huang , Zhishan Liu , Linping Zhao , Zuxiao Chen , Rongrong Zheng , Xiaona Rao , Yuxuan Wei , Xin Chen , Shiying Li . Metal-coordinated oxidative stress amplifier to suppress tumor growth combined with M2 macrophage elimination. Chinese Chemical Letters, 2024, 35(12): 109696-. doi: 10.1016/j.cclet.2024.109696
18. [18]
  Hao Cai , Xiaoyan Wu , Lei Jiang , Feng Yu , Yuxiang Yang , Yan Li , Xian Zhang , Jian Liu , Zijian Li , Hong Bi . Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(4): 108946-. doi: 10.1016/j.cclet.2023.108946
19. [19]
  Shuheng Zhang , Yuanyuan Zhang , Wanyu Wang , Yuzhu Hu , Xinchuan Chen , Bilan Wang , Xiang Gao . A combination strategy of DOX and VEGFR-2 targeted inhibitor based on nanomicelle for enhancing lymphoma therapy. Chinese Chemical Letters, 2024, 35(12): 109658-. doi: 10.1016/j.cclet.2024.109658
20. [20]
  Junfei Yang , Ke Wang , Shuxin Sun , Tianqi Pei , Junxiu Li , Xunwei Gong , Cuixia Zheng , Yun Zhang , Qingling Song , Lei Wang . A "spore-like" oral nanodrug delivery platform for precision targeted therapy of inflammatory bowel disease. Chinese Chemical Letters, 2025, 36(3): 110180-. doi: 10.1016/j.cclet.2024.110180

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(14)
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