Citation: Ruifeng Liang, Yanbei Tu, Peng Hua, Yongzhuo Huang, Meiwan Chen. ROS-responsive micelles co-loaded dexamethasone and pristimerin to restore the homeostasis of the inflammatory microenvironment for rheumatoid arthritis therapy[J]. Chinese Chemical Letters, ;2025, 36(6): 110335. doi: 10.1016/j.cclet.2024.110335 shu

ROS-responsive micelles co-loaded dexamethasone and pristimerin to restore the homeostasis of the inflammatory microenvironment for rheumatoid arthritis therapy

Ruifeng Liang ^{a, 1} ,
Yanbei Tu ^{a, 1} ,
Peng Hua ^a ,
Yongzhuo Huang ^b ,
Meiwan Chen ^{a, *,}

a.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
b.
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China

mwchen@um.edu.mo

Received Date: 27 February 2024
Revised Date: 7 August 2024
Accepted Date: 11 August 2024
Available Online: 12 August 2024

Figures(6)

Invasive fibroblast-like synoviocytes (FLS), inflammatory macrophages and osteoclasts are the main three contributors to rheumatoid arthritis (RA) progression by promoting synovial inflammation and destructing cartilage and bone. Targeting these three cell types for restoring the inflammatory homeostasis microenvironment may be a promising anti-RA strategy. Herein, we prepared a reactive oxygen species (ROS)-responsive micelles (DPTM) to co-load dexamethasone (DEX) and pristimerin (PRI) for RA therapy. This ROS-responsive system exhibits the following advantages: (1) It makes use of the "ELVIS" effect for passive delivery and targeting the ROS environment of RA-related cells to rapidly release the payload drugs DEX and PRI. (2) Compared with free drugs, DPTM showed stronger effect on the inhibition of RA-FLS proliferation and the promotion of RA-FLS apoptosis. Moreover, DPTM could significantly weaken the migration ability of RA-FLS as indicated by the results of wound healing assay and transwell assay. (3) DPTM exerted stronger cellular uptake and anti-inflammatory effect in M1 macrophages. (4) In the model studying receptor activator of nuclear factor kappa-B ligand (RANKL)-induced differentiation of bone marrow-derived macrophages (BMDMs) to osteoclasts, DPTM showed a stronger inhibitory activity on osteoclast formation as compared to free drugs. Taken together, these results highlighted the potential of DPTM for targeted RA therapy via inhibition of RA-FLS abnormal activation, macrophage polarization and osteoclastogenesis.
- Rheumatoid arthritis,
- Micelles,
- Macrophages,
- Fibroblast-like synoviocytes,
- Osteoclastogenesis
1. [1]
  Q. Ding, W. Hu, R. Wang, et al., Signal Transduct. Target. Ther. 8 (2023) 68. doi: 10.1038/s41392-023-01331-9
2. [2]
  G. Simons, J. Caplan, R.L. DiSantostefano, et al., Arthritis Res. Ther. 24 (2022) 55. doi: 10.1186/s13075-021-02707-4
3. [3]
  A.F. Radu, S.G. Bungau, Ageing Res. Rev. 87 (2023) 101927. doi: 10.1016/j.arr.2023.101927
4. [4]
  A.F. Radu, S.G. Bungau, Cells 10 (2021) 2857. doi: 10.3390/cells10112857
5. [5]
  R.I. Ainsworth, D. Hammaker, G. Nygaard, et al., Nat. Commun. 13 (2022) 6221. doi: 10.1038/s41467-022-33785-w
6. [6]
  M.A. Boutet, G. Courties, A. Nerviani, et al., Autoimmun. Rev. 20 (2021) 102758. doi: 10.1016/j.autrev.2021.102758
7. [7]
  K. Yokota, K. Sato, T. Miyazaki, et al., Arthritis Rheumatol. 73 (2021) 1145–1154. doi: 10.1002/art.41666
8. [8]
  N. Komatsu, H. Takayanagi, Nat. Rev. Rheumatol. 18 (2022) 415–429. doi: 10.1038/s41584-022-00793-5
9. [9]
  S. Tardito, G. Martinelli, S. Soldano, et al., Autoimmun. Rev. 18 (2019) 102397. doi: 10.1016/j.autrev.2019.102397
10. [10]
  Z. Wang, J. Wang, T. Lan, et al., Front. Immunol. 14 (2023) 1135384. doi: 10.3389/fimmu.2023.1135384
11. [11]
  Q. Niu, J. Gao, L. Wang, et al., Front. Immunol. 13 (2022) 1034050. doi: 10.3389/fimmu.2022.1034050
12. [12]
  V.M. Dirsch, A.K. Kiemer, H. Wagner, A.M. Vollmar, Eur. J. Pharmacol. 336 (1997) 211–217. doi: 10.1016/S0014-2999(97)01245-4
13. [13]
  D. Qi, H. Liu, X. Sun, et al., Front. Pharmacol. 11 (2020) 621110.
14. [14]
  X. Li, X. Lin, Z. Wu, et al., Drug Des. Dev. Ther. 15 (2021) 61–74. doi: 10.2147/DDDT.S283694
15. [15]
  M. Lorscheider, N. Tsapis, M. Ur-Rehman, et al., J. Control. Release 296 (2019) 179–189. doi: 10.1016/j.jconrel.2019.01.015
16. [16]
  S. Sun, J. Zhang, H. Li, et al., J. Ethnopharmacol. 271 (2021) 113880. doi: 10.1016/j.jep.2021.113880
17. [17]
  Y. Li, Q. Liang, L. Zhou, et al., Acta Biomater. 152 (2022) 406–424. doi: 10.1016/j.actbio.2022.08.054
18. [18]
  F. Yuan, L. Quan, L. Cui, et al., Adv. Drug Deliv. Rev. 64 (2012) 1205–1219. doi: 10.1016/j.addr.2012.03.006
19. [19]
  A.R. Phull, B. Nasir, I.U. Haq, S.J. Kim, Chem. Biol. Interact. 281 (2018) 121–136. doi: 10.1016/j.cbi.2017.12.024
20. [20]
  M.J. Smallwood, A. Nissim, A.R. Knight, et al., Free Radic. Biol. Med. 125 (2018) 3–14. doi: 10.1016/j.freeradbiomed.2018.05.086
21. [21]
  A.P. Croft, J. Campos, K. Jansen, et al., Nature 570 (2019) 246–251. doi: 10.1038/s41586-019-1263-7
22. [22]
  N. Bottini, G.S. Firestein, Nat. Rev. Rheumatol. 9 (2013) 24–33. doi: 10.1038/nrrheum.2012.190
23. [23]
  M. Lv, Q. Liang, Z. Luo, et al., Metabolites 12 (2022) 839. doi: 10.3390/metabo12090839
24. [24]
  C.C. Yang, L.D. Hsiao, H.C. Tseng, et al., J. Inflamm. Res. 13 (2020) 325–341. doi: 10.2147/jir.s252659
25. [25]
  Q. Wang, H. Jiang, Y. Li, et al., Biomaterials 122 (2017) 10–22. doi: 10.1016/j.biomaterials.2017.01.008
26. [26]
  G. Walker, J. Pfeilschifter, U. Otten, D. Kunz, Biochim. Biophys. Acta Gen. Subj. 1568 (2001) 216–224. doi: 10.1016/S0304-4165(01)00223-9
27. [27]
  M. Söderberg, F. Raffalli-Mathieu, M.A. Lang, Mol. Immunol. 44 (2007) 3204–3210. doi: 10.1016/j.molimm.2007.01.029
28. [28]
  H.J. Kim, G.M. Park, J.K. Kim, Arch. Pharmacal. Res. 36 (2013) 495–500. doi: 10.1007/s12272-013-0054-1
29. [29]
  Y. Shen, L. Teng, Y. Qu, et al., J. Ethnopharmacol. 284 (2022) 114791. doi: 10.1016/j.jep.2021.114791
30. [30]
  F. Liu, Y. Liu, S. Zhan, et al., Int. Immunopharmacol. 88 (2020) 106823. doi: 10.1016/j.intimp.2020.106823
31. [31]
  W. Jiao, J. Xu, D. Wu, et al., Phytomedicine 114 (2023) 154741. doi: 10.1016/j.phymed.2023.154741
32. [32]
  W. Sun, N. Meednu, A. Rosenberg, et al., Nat. Commun. 9 (2018) 5127. doi: 10.1038/s41467-018-07626-8
33. [33]
  Y. Tu, L. Tan, T. Lu, et al., Biochem. Pharmacol. 197 (2022) 114912. doi: 10.1016/j.bcp.2022.114912
34. [34]
  Y. Wang, S. Chen, K. Du, et al., J. Ethnopharmacol. 279 (2021) 114368. doi: 10.1016/j.jep.2021.114368
1. [1]
  Dake Liu , Shuyan Liu , Fanlei Hu , Zhongtang Li , Zhongjun Li . N-Glycosylated type Ⅱ collagen peptides as therapeutic saccharide vaccines for rheumatoid arthritis. Chinese Chemical Letters, 2024, 35(5): 108762-. doi: 10.1016/j.cclet.2023.108762
2. [2]
  Chunlei Dai , Liying Wang , Xinru You , Yi Zhao , Zhong Cao , Jun Wu . Coffee-derived self-anti-inflammatory polymer as drug nanocarrier for enhanced rheumatoid arthritis treatment. Chinese Chemical Letters, 2025, 36(3): 109869-. doi: 10.1016/j.cclet.2024.109869
3. [3]
  Fanpeng Shang , Jiantuo Chen . 多视角分析DMPE盘状双层胶束——第38届中国化学奥林匹克(初赛)第4题解析. University Chemistry, 2025, 40(8): 388-393. doi: 10.12461/PKU.DXHX202410034
4. [4]
  Yihan Zhou , Duo Gao , Yaying Wang , Li Liang , Qingyu Zhang , Wenwen Han , Jie Wang , Chunliu Zhu , Xinxin Zhang , Yong Gan . Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(6): 108967-. doi: 10.1016/j.cclet.2023.108967
5. [5]
  Rui Li , Ruijie Lu , Libin Yang , Jianwen Li , Zige Guo , Qiquan Yan , Mengjun Li , Yazhuo Ni , Keying Chen , Yaoyang Li , Bo Xu , Mengzhen Cui , Zhan Li , Zhiying Zhao . Immobilization of chitosan nano-hydroxyapatite alendronate composite microspheres on polyetheretherketone surface to enhance osseointegration by inhibiting osteoclastogenesis and promoting osteogenesis. Chinese Chemical Letters, 2025, 36(4): 110242-. doi: 10.1016/j.cclet.2024.110242
6. [6]
  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
7. [7]
  Jiahao Liu , Peng Liu , Junhong Duan , Qiongxuan Xie , Jie Feng , Hongpei Tan , Ze Mi , Ying Li , Yunjie Liao , Pengfei Rong , Wenhu Zhou , Xiang Gao . Macrophages-mediated tumor accumulation and deep penetration of bismuth/manganese biomineralized nanoparticles for enhanced radiotherapy. Chinese Chemical Letters, 2024, 35(12): 109632-. doi: 10.1016/j.cclet.2024.109632
8. [8]
  Tong Zhang , Chao Sun , Shubin Yang , Zimin Cai , Sifeng Zhu , Wendian Liu , Yun Luan , Cheng Wang . Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis. Chinese Chemical Letters, 2024, 35(8): 109248-. doi: 10.1016/j.cclet.2023.109248
9. [9]
  Mengjuan Sun , Muye Zhou , Yifang Xiao , Hailei Tang , Jinhua Chen , Ruitao Zhang , Chunjiayu Li , Qi Ya , Qian Chen , Jiasheng Tu , Qiyue Wang , Chunmeng Sun . Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy. Chinese Chemical Letters, 2024, 35(7): 109110-. doi: 10.1016/j.cclet.2023.109110
10. [10]
  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
11. [11]
  Yu Qin , Mingyang Huang , Chenlu Huang , Hannah L. Perry , Linhua Zhang , Dunwan Zhu . O₂-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma. Chinese Chemical Letters, 2024, 35(7): 109171-. doi: 10.1016/j.cclet.2023.109171
12. [12]
  Hongyi Huang , Siyao Che , Wenjie Zhou , Yunchu Zhang , Weiling Zhuo , Xijing Yang , Songping Zheng , Jiagang Liu , Xiang Gao . Apatinib potentiates doxorubicin with cRGD-functionalized pH-sensitive micelles against glioma. Chinese Chemical Letters, 2025, 36(5): 110084-. doi: 10.1016/j.cclet.2024.110084
13. [13]
  Yuanyuan Zeng , Fang Liu , Jun Wang , Bianfei Shao , Tao He , Zhongzheng Xiang , Yan Wang , Shunyao Zhu , Tian Yang , Siting Yu , Changyang Gong , Lei Liu . Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor. Chinese Chemical Letters, 2025, 36(2): 109734-. doi: 10.1016/j.cclet.2024.109734
14. [14]
  Li Fu , Ziye Su , Shuyang Wu , Yanfen Cheng , Chuan Hu , Jinming Zhang . Redox-responsive hyaluronic acid-celastrol prodrug micelles with glycyrrhetinic acid co-delivery for tumor combination therapy. Chinese Chemical Letters, 2025, 36(5): 110227-. doi: 10.1016/j.cclet.2024.110227
15. [15]
  Yixin Sun , Keke Yu , Xiuchun Guo , Lanlan Zong , Zhonggui He , Xiaohui Pu . Three-in-one reduction and acid-ignited micelles amplify antitumor efficacy via precise synergistic delivery of paclitaxel and naringenin. Chinese Chemical Letters, 2025, 36(6): 110393-. doi: 10.1016/j.cclet.2024.110393
16. [16]
  Jiayao Li , Xinru Peng , Shiwei Yin , Changwei Wang , Yirong Mo . Metastability of π-π stacking between the closed-shell ions of like charges. Chinese Journal of Structural Chemistry, 2024, 43(5): 100213-100213. doi: 10.1016/j.cjsc.2023.100213
17. [17]
  Wenying Cui , Zhetong Jin , Wentao Fu , Chengshuo Shen . Flag-hinge-like highly luminescent chiral nanographenes with twist geometry. Chinese Chemical Letters, 2024, 35(11): 109667-. doi: 10.1016/j.cclet.2024.109667
18. [18]
  Yiqian Jiang , Zihan Yang , Xiuru Bi , Nan Yao , Peiqing Zhao , Xu Meng . Mediated electron transfer process in α-MnO₂ catalyzed Fenton-like reaction for oxytetracycline degradation. Chinese Chemical Letters, 2024, 35(8): 109331-. doi: 10.1016/j.cclet.2023.109331
19. [19]
  Jia-Li Xie , Tian-Jin Xie , Yu-Jie Luo , Kai Mao , Cheng-Zhi Huang , Yuan-Fang Li , Shu-Jun Zhen . Octopus-like DNA nanostructure coupled with graphene oxide enhanced fluorescence anisotropy for hepatitis B virus DNA detection. Chinese Chemical Letters, 2024, 35(6): 109137-. doi: 10.1016/j.cclet.2023.109137
20. [20]
  Shiyu Pan , Bo Cao , Deling Yuan , Tifeng Jiao , Qingrui Zhang , Shoufeng Tang . Complexes of cupric ion and tartaric acid enhanced calcium peroxide Fenton-like reaction for metronidazole degradation. Chinese Chemical Letters, 2024, 35(7): 109185-. doi: 10.1016/j.cclet.2023.109185

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(398)
HTML views(11)

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