Citation: Zhongxin Duan, Yue Wang, Yunchu Zhang, Xia Liu, Wanyu Wang, Hua Li, Qingyang Lu, Chao You, Yongzhong Cheng, Cong Wu, Xiang Gao. Intranasal pterostilbene nanoparticles delivery alleviates neuroinflammation and brain injury after intracerebral hemorrhage[J]. Chinese Chemical Letters, ;2026, 37(5): 111248. doi: 10.1016/j.cclet.2025.111248 shu

Intranasal pterostilbene nanoparticles delivery alleviates neuroinflammation and brain injury after intracerebral hemorrhage

Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China

wu_cong38@aliyun.com

xianggao@scu.edu.cn

Received Date: 8 February 2025
Revised Date: 16 April 2025
Accepted Date: 21 April 2025
Available Online: 22 April 2025

Figures(5)

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and poor prognosis among survivors. Neuroinflammation after ICH plays a critical role in both secondary brain injury and repair. In the early stages of ICH, excessive activation of microglia triggers pro-inflammation, leading to the release of various pro-inflammatory cytokines that exacerbate neuronal damage and worsen neurological deficits. Pterostilbene (PTE), a natural polyphenol with potent anti-inflammatory and antioxidant properties, is an ideal neuroprotective agent. However, its clinical application is limited by poor bioavailability and low blood-brain barrier (BBB) penetrability following oral administration. Here, we developed PTE-loaded methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles (PTE-NPs) to enhance the bioavailability of PTE and performed an intranasal delivery strategy for non-invasive and efficient transport to the ICH lesion. PTE-NPs significantly suppressed pro-inflammatory microglia activation and cytokine release, thereby reducing inflammation-mediated neuronal damage in the peri–hematomal region. In the two ICH mouse models, PTE-NPs demonstrated significant therapeutic efficacy in improving neurological function with good biosafety. This study provides a potential therapeutic strategy for the treatment of ICH and its future clinical translation.
- Nanoparticles,
- Blood-brain barriers penetrability,
- Intranasal delivery,
- Intracerebral hemorrhage,
- Neuroinflammation
1. [1]
  L. Puy, A.R. Parry-Jones, E.C. Sandset, et al., Nat. Rev. Dis. Primers 9 (2023) 14. doi: 10.1038/s41572-023-00424-7
2. [2]
  J. Magid-Bernstein, R. Girard, S. Polster, et al., Circ. Res. 130 (2022) 1204–1229. doi: 10.1161/circresaha.121.319949
3. [3]
  K.N. Sheth, N. Engl. J. Med. 387 (2022) 1589–1596. doi: 10.1056/nejmra2201449
4. [4]
  C.J. van Asch, M.J. Luitse, G.J. Rinkel, et al., Lancet Neurol. 9 (2010) 167–176. doi: 10.1016/S1474-4422(09)70340-0
5. [5]
  S.J. An, T.J. Kim, B.W. Yoon, J. Stroke 19 (2017) 3–10. doi: 10.5853/jos.2016.00864
6. [6]
  B.M. Hansen, O.G. Nilsson, H. Anderson, et al., J. Neurol. Neurosurg. Psychiatry 84 (2013) 1150–1155. doi: 10.1136/jnnp-2013-305200
7. [7]
  S.M. Greenberg, W.C. Ziai, C. Cordonnier, et al., Stroke 53 (2022) e282–e361.
8. [8]
  V.L. Feigin, B.A. Stark, C.O. Johnson, et al., Lancet Neurol. 20 (2021) 795–820. doi: 10.1016/S1474-4422(21)00252-0
9. [9]
  H. Ren, R. Han, X. Chen, et al., J. Cereb. Blood Flow Metab. 40 (2020) 1752–1768. doi: 10.1177/0271678x20923551
10. [10]
  M. Xue, V.W. Yong, Lancet Neurol. 19 (2020) 1023–1032. doi: 10.1016/S1474-4422(20)30364-1
11. [11]
  H. Chu, C. Huang, Z. Zhou, et al., Int. J. Surg. 109 (2023) 266–276. doi: 10.1097/js9.0000000000000191
12. [12]
  E.R. Bader, T.A. Pana, R.S. Barlas, et al., J. Neurol. 269 (2022) 6330–6341. doi: 10.1007/s00415-022-11284-8
13. [13]
  T. Shichita, H. Ooboshi, A. Yoshimura, Nat. Rev. Neurosci. 24 (2023) 299–312. doi: 10.1038/s41583-023-00690-0
14. [14]
  Q. Li, X. Lan, X. Han, et al., Brain Behav. Immun. 94 (2021) 437–457. doi: 10.1016/j.bbi.2021.02.001
15. [15]
  C. Xie, J. Liao, N. Zhang, et al., Chin. Chem. Lett. 35 (2024) 109149. doi: 10.1016/j.cclet.2023.109149
16. [16]
  X. Li, X. Gao, W. Zhang, et al., Cell Death Dis. 13 (2022) 33. doi: 10.1038/s41419-021-04424-x
17. [17]
  W. Chen, Y. Zhang, X. Zhai, et al., J. Cereb. Blood Flow Metab. (2022) 1579–1596. doi: 10.1177/0271678x221098841
18. [18]
  H. Kim, K.H. Seo, W. Yokoyama, J. Agric. Food Chem. 68 (2020) 12836–12841. doi: 10.1021/acs.jafc.0c00070
19. [19]
  B.J. Dutta, P.S. Rakshe, N. Maurya, et al., Ageing Res. Rev. 92 (2023) 102125. doi: 10.1016/j.arr.2023.102125
20. [20]
  Z.H. Yang, Y.J. Liu, W.K. Ban, et al., Food Funct. 14 (2023) 8291–8308. doi: 10.1039/d3fo02639f
21. [21]
  Y. Chen, W. He, J. Qiu, et al., Cell Mol. Biol. Lett. 29 (2024) 114. doi: 10.1186/s11658-024-00634-1
22. [22]
  J. Liu, J. Xu, L. Jia, et al., Int. J. Pharm. 655 (2024) 124002. doi: 10.1016/j.ijpharm.2024.124002
23. [23]
  J. Xu, J. Liu, Q. Li, et al., Phytomedicine 119 (2023) 155011. doi: 10.1016/j.phymed.2023.155011
24. [24]
  F. Pacifici, C. Salimei, D. Pastore, et al., Int. J. Mol. Sci. 23 (2022) 3110. doi: 10.3390/ijms23063110
25. [25]
  R.W. Dellinger, H.E. Holmes, T. Hu-Seliger, et al., Hepatology 78 (2023) 863–877. doi: 10.1002/hep.32778
26. [26]
  J.B. Jensen, O.L. Dollerup, A.B. Moller, et al., JCI Insight 7 (2022) e158314. doi: 10.1172/jci.insight.158314
27. [27]
  M. Waszczuk, S.E. Bianchi, V. Pittol, et al., Int. J. Pharm. 635 (2023) 122736. doi: 10.1016/j.ijpharm.2023.122736
28. [28]
  B. Wang, S. Hu, Y. Teng, et al., Signal Transduct. Target. Ther. 9 (2024) 200. doi: 10.1201/9781003483755-20
29. [29]
  H. Wu, Y. Wang, Z. Ren, et al., Chin. Chem. Lett. 36 (2025) 109996. doi: 10.1016/j.cclet.2024.109996
30. [30]
  J.K. Patra, G. Das, L.F. Fraceto, et al., J. Nanobiotechnology 16 (2018) 71.
31. [31]
  J. Li, M. Zheng, O. Shimoni, et al., Adv. Sci. 8 (2021) e2101090. doi: 10.1002/advs.202101090
32. [32]
  C.P. Costa, J.N. Moreira, J.M. Sousa Lobo, et al., Acta Pharm. Sin. B 11 (2021) 925–940. doi: 10.1016/j.apsb.2021.02.012
33. [33]
  H. Shen, N. Aggarwal, B. Cui, et al., Cell 188 (2025) 1545–1562. doi: 10.1016/j.cell.2025.01.017
34. [34]
  D. Wu, Q. Chen, X. Chen, et al., Signal Transduct. Target. Ther. 8 (2023) 217.
35. [35]
  A.A. Yakubova, K.A. Mitusova, A. Darwish, et al., J. Control. Release 359 (2023) 400–414. doi: 10.1016/j.jconrel.2023.06.012
36. [36]
  Y. Wang, P. Tang, W. Tu, et al., Chin. Chem. Lett. 36 (2025) 109955. doi: 10.1016/j.cclet.2024.109955
37. [37]
  C. Wei, C. Chen, S. Li, et al., Redox Biol. 80 (2025) 103487. doi: 10.1016/j.redox.2024.103487
38. [38]
  X. Lan, X. Han, Q. Li, et al., Nat. Rev. Neurol. 13 (2017) 420–433. doi: 10.1038/nrneurol.2017.69
1. [1]
  Lian Jin , Juan Zhang , Libo Nie , Yan Deng , Ghulam Jilany Khana , Nongyue He . Chitosan nanoparticles act as promising carriers of microRNAs to brain cells in neurodegenerative diseases. Chinese Chemical Letters, 2025, 36(10): 110774-. doi: 10.1016/j.cclet.2024.110774
2. [2]
  Yuwen Zhu , Xiang Deng , Yan Wu , Baode Shen , Lingyu Hang , Yuye Xue , Hailong Yuan . Formation mechanism of herpetrione self-assembled nanoparticles based on pH-driven method. Chinese Chemical Letters, 2025, 36(1): 109733-. doi: 10.1016/j.cclet.2024.109733
3. [3]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
4. [4]
  Liangyu Zhang , Lei Lei , Zhuangzhuang Zhao , Guizhi Yang , Kaitao Wang , Liying Wang , Ningxin Zhang , Yanjia Ai , Xinqing Ma , Guannan Liu , Meng Zhao , Jun Wu , Dongjun Lin , Chun Chen . Enhanced venetoclax delivery using l-phenylalanine nanocarriers in acute myeloid leukemia treatment. Chinese Chemical Letters, 2025, 36(6): 110316-. doi: 10.1016/j.cclet.2024.110316
5. [5]
  Bohan Chen , Liming Gong , Jing Feng , Mingji Jin , Liqing Chen , Zhonggao Gao , Wei Huang . Research advances of nanoparticles for CAR-T therapy in solid tumors. Chinese Chemical Letters, 2024, 35(9): 109432-. doi: 10.1016/j.cclet.2023.109432
6. [6]
  Wei Su , Xiaoyan Luo , Peiyuan Li , Ying Zhang , Chenxiang Lin , Kang Wang , Jianzhuang Jiang . Phthalocyanine self-assembled nanoparticles for type Ⅰ photodynamic antibacterial therapy. Chinese Chemical Letters, 2024, 35(12): 109522-. doi: 10.1016/j.cclet.2024.109522
7. [7]
  Yiran Tao , Chunlei Dai , Zhaoxiang Xie , Xinru You , Kaiwen Li , Jun Wu , Hai Huang . Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer. Chinese Chemical Letters, 2024, 35(8): 109170-. doi: 10.1016/j.cclet.2023.109170
8. [8]
  Tianxia Chen , Yunhui Chen , Weiwei Li , Peipei Cen , Yan Guo , Jin Zhang , Cunding Kong , Xiangyu Liu . Fabricating AuAg-nanoparticles/ZIF-8 composites for selective detection and efficient extraction of dinitroaniline pesticides. Chinese Chemical Letters, 2025, 36(8): 110214-. doi: 10.1016/j.cclet.2024.110214
9. [9]
  Yihao Zhang , Yang Jiao , Xianchao Jia , Qiaojia Guo , Chunying Duan . Highly effective self-assembled porphyrin MOCs nanomaterials for enhanced photodynamic therapy in tumor. Chinese Chemical Letters, 2024, 35(5): 108748-. doi: 10.1016/j.cclet.2023.108748
10. [10]
  Yixin Zhang , Ting Wang , Jixiang Zhang , Pengyu Lu , Neng Shi , Liqiang Zhang , Weiran Zhu , Nongyue He . Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane. Chinese Chemical Letters, 2024, 35(4): 108619-. doi: 10.1016/j.cclet.2023.108619
11. [11]
  Keyang Li , Yanan Wang , Yatao Xu , Guohua Shi , Sixian Wei , Xue Zhang , Baomei Zhang , Qiang Jia , Huanhua Xu , Liangmin Yu , Jun Wu , Zhiyu He . Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation. Chinese Chemical Letters, 2024, 35(10): 109511-. doi: 10.1016/j.cclet.2024.109511
12. [12]
  Fereshte Hassanzadeh-Afruzi , Mina Azizi , Iman Zare , Ehsan Nazarzadeh Zare , Anwarul Hasan , Siavash Iravani , Pooyan Makvandi , Yi Xu . Advanced metal-organic frameworks-polymer platforms for accelerated dermal wound healing. Chinese Chemical Letters, 2024, 35(11): 109564-. doi: 10.1016/j.cclet.2024.109564
13. [13]
  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
14. [14]
  Mengdie Li , Shundong Cai , Hongjin Li , Yuhang Cheng , Jinfa Ye , Lang Ke , Yun Han , Min Su , Gang Liu , Chengchao Chu . Nanotherapeutics for ocular posterior segment diseases therapy: Towards its advances and challenges. Chinese Chemical Letters, 2026, 37(5): 111392-. doi: 10.1016/j.cclet.2025.111392
15. [15]
  Guanlong Li , Zhuoyan Li , Yan Sun , Tiange Bu , Shaochuan Chen , Leixin Yang , Zhi Li , Wenyue Mao , Yanpeng Jia . Advances in CNS drug delivery strategies to cross the blood-brain barrier. Chinese Chemical Letters, 2026, 37(1): 111524-. doi: 10.1016/j.cclet.2025.111524
16. [16]
  Jialin Guo , Mingrui Gu , Yahui Chen , Tao Xiong , Yiyang Zhang , Simin Chen , Mingle Li , Xiaoqiang Chen , Xiaojun Peng . Nucleic acid delivery by lipid nanoparticles for organ targeting. Chinese Chemical Letters, 2025, 36(11): 110849-. doi: 10.1016/j.cclet.2025.110849
17. [17]
  Han Wu , Yumei Wang , Zekai Ren , Hailin Cong , Youqing Shen , Bing Yu . The nanocarrier strategy for crossing the blood-brain barrier in glioma therapy. Chinese Chemical Letters, 2025, 36(4): 109996-. doi: 10.1016/j.cclet.2024.109996
18. [18]
  Shushan Mo , Zhaoshuo Wang , Dandan Ding , Zhengzheng Yan , Yunlu Dai , Jinchao Zhang , Huifang Liu , Tianjiao Liang , Jianfei Tong , Zhenhua Li , Xueyi Wang . The synthesis and evaluation of novel BPA derivatives for enhanced blood-brain barrier penetration and boron neutron capture therapy. Chinese Chemical Letters, 2025, 36(5): 110190-. doi: 10.1016/j.cclet.2024.110190
19. [19]
  Luyu Zhang , Zirong Dong , Shuai Yu , Guangyue Li , Weiwen Kong , Wenjuan Liu , Haisheng He , Yi Lu , Wei Wu , Jianping Qi . Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes (CLNs) for enhanced intranasal siRNA delivery. Chinese Chemical Letters, 2024, 35(7): 109101-. doi: 10.1016/j.cclet.2023.109101
20. [20]
  Haoran Xu , Jiaqi Fan , Jiwei Liu , Qi Wei , Ruoshui Li , Pengcheng Yuan , Bing Xiao , Ying Piao , Wenjing Sun , Jiajia Xiang , Shiqun Shao , Zhuxian Zhou , Youqing Shen , Nigel K.H. Slater , Jianbin Tang . Tetra-branched ionizable lipids enhance the stability and transfection efficiency of lipid nanoparticles for mRNA delivery. Chinese Chemical Letters, 2025, 36(11): 110833-. doi: 10.1016/j.cclet.2025.110833

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(16)
HTML views(3)

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