Citation: Liqing Chen, Zheming Zhang, Yanhong Liu, Chenfei Liu, Congcong Xiao, Liming Gong, Mingji Jin, Zhonggao Gao, Wei Huang. Systemically intravenous siRNA delivery into brain with a targeting and efficient polypeptide carrier and its evaluation on anti-glioma efficacy[J]. Chinese Chemical Letters, ;2025, 36(3): 110228. doi: 10.1016/j.cclet.2024.110228 shu

Systemically intravenous siRNA delivery into brain with a targeting and efficient polypeptide carrier and its evaluation on anti-glioma efficacy

Liqing Chen ^{a, b, 1} ,
Zheming Zhang ^{a, b, 1} ,
Yanhong Liu ^{a, b} ,
Chenfei Liu ^{a, b} ,
Congcong Xiao ^{a, b} ,
Liming Gong ^{a, b} ,
Mingji Jin ^{a, b} ,
Zhonggao Gao ^{a, b, *,} ,
Wei Huang ^{a, b, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

zggao@imm.ac.cn

huangwei@imm.ac.cn

Received Date: 21 April 2024
Revised Date: 30 June 2024
Accepted Date: 8 July 2024
Available Online: 8 July 2024

Figures(5)

Gliomas are the most common intracranial tumors with poor survival and high mortality. Furthermore, the clinical efficacy of current drugs is still not ideal; despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients. RNAi-based therapy presents a novel disease-related gene targeting therapy, including otherwise undruggable genes, and generates therapeutic options. However, the therapeutic effect of siRNA is hindered by multiple biological barriers, primarily the blood-brain barrier (BBB). A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon. RDP, a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein (RVG), possesses an N-type acetylcholine receptor (nAChR)-binding efficiency similar to that of RVG29. Given its lower cost and small particle size when used as a ligand, RDP should be extensively evaluated. First, we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide (designated RDP-5R) as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo. The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB- and glioma cell-targeting. The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application, desirable glioma-targeting effects, and therapeutic efficiency. As a novel and efficient polypeptide carrier, RDP-based polypeptides hold great promise as a noninvasive, safe, and efficient treatment for various brain diseases.
- 15-Amino-acid peptide,
- Glioma,
- Brain targeting,
- Gene silencing,
- Transvascular delivery
1. [1]
  H. Yang, W. Li, Y. Xun, A.P. Yang, H. You, Mol. Ther. Oncolytics. 21 (2021) 1–14.
2. [2]
  Z.Y. Lin, R.W. Yang, K.S. Li, et al., BMC Neurol. 20 (2020) 310.
3. [3]
  T. Tykocki, M. Eltayeb, J. Clin. Neurosci. 54 (2018) 7–13.
4. [4]
  A. Aigner, D. Kögel, Nanomedicine 13 (2018) 89–103. doi: 10.2217/nnm-2017-0230
5. [5]
  C. Adida, P.L. Crotty, J. McGrath, D. Berrebi, J. Diebold, D.C. Altieri, Am. J. Pathol. 152 (1998) 43–49.
6. [6]
  G. Ambrosini, C. Adida, D.C. Altieri, Nat. Med. 3 (1997) 917–921.
7. [7]
  L.L. Kusner, M.J. Ciesielski, A. Marx, H.J. Kaminski, R.A. Fenstermaker, PLoS ONE 9 (2014) e102231. doi: 10.1371/journal.pone.0102231
8. [8]
  M. Zheng, W. Tao, Y. Zou, O.C. Farokhzad, B.Y. Shi, Trends Biotechnol. 36 (2018) 562–75.
9. [9]
  D. Karra, R. Dahm, J. Neurosci. 30 (2010) 6171–6177.
10. [10]
  J.M. Bergen, I.K. Park, P.J. Horner, S.H. Pun, Pharm Res. 25 (2008) 983–998. doi: 10.1007/s11095-007-9439-5
11. [11]
  I. Mortimer, P. Tam, I. MacLachlan, et al., Gene Ther. 6 (1999) 403–411. doi: 10.1038/sj.gt.3300837
12. [12]
  Y.Y. Kuang, S. An, Y.B. Guo, et al., Int. J. Pharm. 454 (2013) 11–20.
13. [13]
  Y.Y. Kuang, X.T. Jiang, Y. Zhang, et al., Mol. Pharm. 13 (2016) 1599–1607. doi: 10.1021/acs.molpharmaceut.6b00051
14. [14]
  L. Wei, X.Y. Guo, T. Yang, et al., Int. J. Pharm. 510 (2016) 394–405.
15. [15]
  L. Wang, Y.W. Hao, H.X. Li, et al., J. Drug Target 23 (2015) 832–846. doi: 10.3109/1061186X.2015.1025077
16. [16]
  S. An, D.S. He, E. Wagner, C. Jiang, Small 11 (2015) 5142–5150. doi: 10.1002/smll.201501167
17. [17]
  P. Kumar, H.Q. Wu, J.L. McBride, et al., Nature 448 (2007) 39–43. doi: 10.1038/nature05901
18. [18]
  C. Gotti, F. Clementi, Prog. Neurobiol. 74 (2004) 363–396.
19. [19]
  M.K. Qu, Q. Lin, S.S. He, et al., J. Control. Release 277 (2018) 173–182.
20. [20]
  Y. Han, C.H. Gao, H. Wang, et al., Bioact. Mater. 6 (2021) 529–542.
21. [21]
  C.Q. Qiao, R.L. Zhang, Y.D. Wang, et al., Angew. Chem. Int. Ed. 59 (2020) 16982–16988. doi: 10.1002/anie.202007474
22. [22]
  S.B. Ruan, Y. Zhou, X.G. Jiang, H.L. Gao, Adv. Sci. 8 (2021) 2004025.
23. [23]
  J.L. Yang, X.F. Zhang, X.J. Chen, L. Wang, G.D. Yang, Mol. Ther. Nucleic Acids 7(2017) 278–287.
24. [24]
  J.M. Cooper, P.B. Wiklander, J.Z. Nordin, et al., Mov. Disord. 29(2014) 1476–1485. doi: 10.1002/mds.25978
25. [25]
  J.W. Cui, Y.X. Xu, H.Y. Tu, et al., Acta Pharm. Sin. B 12 (2022) 1100–1125.
26. [26]
  T.I. Terpinskaya, A.V. Osipov, E.V. Kryukova, et al., Mar. Drugs 19 (2021) 118. doi: 10.3390/md19020118
27. [27]
  S. Danthi, R.T. Boyd, Neurosci. Lett. 400 (2006) 63–68.
28. [28]
  C. Thongbamrer, W. Roobsoong, J. Sattabongkot, P. Opanasopit, B.E. Yingyongnarongkul, ChemBioChem 23(2022) e202100672.
29. [29]
  F. Li, N.C. Song, Y.H. Dong, et al., Angew. Chem. Int. Ed. 61 (2022) e202116569.
30. [30]
  S. Salatin, S. Maleki Dizaj, A. Yari Khosroushahi, Cell. Biol. Int. 39 (2015) 881–890. doi: 10.1002/cbin.10459
31. [31]
  X.T. Qi, J.S. Zhan, L.M. Xiao, et al., Neurochem. Res. 42 (2017) 1847–1863. doi: 10.1007/s11064-017-2272-2
32. [32]
  C.D. Arvanitis, G.B. Ferraro, R.K. Jain, Nat. Rev. Cancer 20 (2020) 26–41. doi: 10.1038/s41568-019-0205-x
33. [33]
  L. Chen, D. Zeng, N. Xu, et al., ACS Appl. Mater. Interfaces 11 (2019) 41889–41897. doi: 10.1021/acsami.9b14046
34. [34]
  D. Janigro, S.M. Leaman, K.A. Stanness, Pharm. Sci. Technol. Today 2 (1999) 7–12.
35. [35]
  M.A. Subhan, S.S.K. Yalamarty, N. Filipczak, F. Parveen, V.P. Torchilin, J. Pers. Med. 11 (2021) 571. doi: 10.3390/jpm11060571
36. [36]
  R. Liu, C. Luo, Z. Pang, et al., Chin. Chem. Lett. 34 (2023) 107518.
37. [37]
  H. Wu, Y.M. Wang, Z.K. Ren, et al., Chin. Chem. Lett. (2024), doi:10.1016/j.cclet.2024.109996. doi: 10.1016/j.cclet.2024.109996
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9. [9]
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