Citation: Rui Li, Mengxi Zhu, Xiwen Hu, Jiaxuan Chen, Fei Yu, Stefan Barth, Lu Sun, Huining He. Overcoming endosomal/lysosomal barriers: Advanced strategies for cytosolic siRNA delivery[J]. Chinese Chemical Letters, ;2025, 36(9): 110736. doi: 10.1016/j.cclet.2024.110736 shu

Overcoming endosomal/lysosomal barriers: Advanced strategies for cytosolic siRNA delivery

Rui Li ^{b, 1} ,
Mengxi Zhu ^{b, 1} ,
Xiwen Hu ^{a, 1} ,
Jiaxuan Chen ^b ,
Fei Yu ^b ,
Stefan Barth ^c ,
Lu Sun ^{b, *,} ,
Huining He ^{a, b, *,}

a.
International Joint Laboratory of Ocular Diseases, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China
b.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
c.
Medical Biotechnology and Immunotherapy Research Unit, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa

sunlu@tmu.edu.cn

hehuining@tmu.edu.cn

Received Date: 29 August 2024
Revised Date: 2 December 2024
Accepted Date: 6 December 2024
Available Online: 9 December 2024

Figures(7)

Small interfering RNAs (siRNA) provide a novel and highly specific therapy due to their ability to effectively silence target genes, to date six siRNA therapeutics are approved for clinical use. Even so, some critical challenges remain to overcome in the therapeutic application of siRNAs, with delivery issues at the forefront. Among them, endo/lysosomal barrier is one of the important but often-neglected limitations hindering the delivery of siRNA therapeutics. In this review, we summarize the promising strategies that facilitate siRNAs overcoming endo/lysosomal barriers based on the cellular uptake and intracellular transport pathways, including promoting escape once endocytosis into the endo/lysosomes and bypassing lysosomes via endosome-Golgi-endoplasmic reticulum (ER) pathway or nonendocytosis pathway, and discuss the principal considerations and the future directions of promoting endo/lysosomal escape in the development of therapeutic siRNAs.
- siRNA,
- Endosomal/lysosomal escape,
- Cytosolic delivery,
- Endosome-Golgi-ER pathway,
- Nonendocytosis pathway
1. [1]
  R.L. Setten, J.J. Rossi, S.P. Han, Nat. Rev. Drug. Discov. 18 (2019) 421–446. doi: 10.1038/s41573-019-0017-4
2. [2]
  A. Fire, S. Xu, M.K. Montgomery, et al., Nature 391 (1998) 806–811. doi: 10.1038/35888
3. [3]
  S.M. Elbashir, J. Harborth, W. Lendeckel, et al., Nature 411 (2001) 494–498. doi: 10.1038/35078107
4. [4]
  M.A. Ashfaq, V.D. Kumar, P.S.S. Reddy, et al., J. Biosci. 45 (2020) 128. doi: 10.1007/s12038-020-00098-3
5. [5]
  M. Friedrich, A. Aigner, BioDrugs 36 (2022) 549–571. doi: 10.1007/s40259-022-00549-3
6. [6]
  Q. Tang, A. Khvorova, Nat. Rev. Drug Discov. 23 (2024) 341–364. doi: 10.1038/s41573-024-00912-9
7. [7]
  D. Adams, A. Gonzalez-Duarte, W.D. O'Riordan, et al., N. Engl. J. Med. 379 (2018) 11–21. doi: 10.1056/nejmoa1716153
8. [8]
  J.R. Androsavich, Nat. Rev. Drug Discov. 23 (2024) 421–444. doi: 10.1038/s41573-024-00943-2
9. [9]
  B. Hu, L. Zhong, Y. Weng, et al., Signal Transduct. Target. Ther. 5 (2020) 101. doi: 10.1038/s41392-020-0207-x
10. [10]
  L. Zhang, Z. Dong, S. Yu, et al., Chin. Chem. Lett. 35 (2024) 109101. doi: 10.1016/j.cclet.2023.109101
11. [11]
  S. Schenk, G.J. Schoenhals, G. de Souza, M. Mann, BMC Med. Genom. 1 (2008) 41. doi: 10.1186/1755-8794-1-41
12. [12]
  B. Godinho, E.G. Knox, S. Hildebrand, et al., Mol. Ther. Nucleic. Acids 29 (2022) 116–132. doi: 10.1016/j.omtn.2022.06.005
13. [13]
  A. Biscans, A. Coles, R. Haraszti, et al., Nucleic Acids Res. 47 (2019) 1082–1096. doi: 10.1093/nar/gky1239
14. [14]
  J. Zhang, B. Chen, C. Gan, et al., Int. J. Nanomed. 18 (2023) 7605–7635. doi: 10.2147/ijn.s436038
15. [15]
  S.F. Dowdy, RNA 29 (2023) 396–401. doi: 10.1261/rna.079507.122
16. [16]
  S. Guo, M. Zhang, Y. Huang, Trends Mol. Med. 30 (2024) 13–24.
17. [17]
  K. Paunovska, D. Loughrey, J.E. Dahlman, Nat. Rev. Genet. 23 (2022) 265–280. doi: 10.1038/s41576-021-00439-4
18. [18]
  Y. Jia, X. Wang, L. Li, et al., Adv. Mater. 36 (2024) e2305300. doi: 10.1002/adma.202305300
19. [19]
  K. Alamoudi, P. Martins, J.G. Croissant, et al., Nanomedicine 12 (2017) 1421–1433. doi: 10.2217/nnm-2017-0021
20. [20]
  J.P. Bost, H. Barriga, M.N. Holme, et al., ACS Nano 15 (2021) 13993–14021. doi: 10.1021/acsnano.1c05099
21. [21]
  B. Hu, S. Kong, Y. Weng, et al., Chin. Chem. Lett. 34 (2023) 108210. doi: 10.1016/j.cclet.2023.108210
22. [22]
  F. Hu, J. Qi, Y. Lu, H. He, W. Wu, Chin. Chem. Lett. 34 (2023) 108250. doi: 10.1016/j.cclet.2023.108250
23. [23]
  M. Sousa de Almeida, E. Susnik, B. Drasler, et al., Chem. Soc. Rev. 50 (2021) 5397–5434. doi: 10.1039/d0cs01127d
24. [24]
  X. Wang, Y. Yin, H. Zhou, et al., Exploration 5 (2025) 20240036. doi: 10.1002/EXP.20240036
25. [25]
  J. Gilleron, W. Querbes, A. Zeigerer, et al., Nat. Biotechnol. 31 (2013) 638–646. doi: 10.1038/nbt.2612
26. [26]
  Y. Xia, M. Guo, T. Xu, et al., Int. J. Nanomed. 13 (2018) 1539–1552. doi: 10.2147/ijn.s157519
27. [27]
  E. Linnane, S. Haddad, F. Melle, Z. Mei, D. Fairen-Jimenez, Chem. Soc. Rev. 51 (2022) 6065–6086. doi: 10.1039/d0cs01414a
28. [28]
  A.L. Kiss, E. Botos, J. Cell. Mol. Med. 13 (2009) 1228–1237. doi: 10.1111/j.1582-4934.2009.00754.x
29. [29]
  Y. Song, Y. Wu, L. Xu, et al., ACS Nano 15 (2021) 8267–8282. doi: 10.1021/acsnano.0c08596
30. [30]
  S. Patel, J. Kim, M. Herrera, et al., Adv. Drug Deliv. Rev. 144 (2019) 90–111. doi: 10.1016/j.addr.2019.08.004
31. [31]
  M. Sako, F. Song, A. Okamoto, et al., Int. J. Pharm. 569 (2019) 118606. doi: 10.1016/j.ijpharm.2019.118606
32. [32]
  M. Lu, X. Zhao, H. Xing, et al., Int. J. Pharm. 550 (2018) 100–113. doi: 10.1016/j.ijpharm.2018.08.040
33. [33]
  J. Sun, C. Qiu, Y. Diao, et al., Mol. Ther. Nucleic. Acids 10 (2018) 75–90. doi: 10.1016/j.omtn.2017.11.002
34. [34]
  C. Qiu, F. Xia, J. Zhang, et al., Research 6 (2023) 0148. doi: 10.34133/research.0148
35. [35]
  E. Fakhr, F. Zare, L. Teimoori-Toolabi, Cancer Gene Ther. 23 (2016) 73–82. doi: 10.1038/cgt.2016.4
36. [36]
  J. Zhu, M. Qiao, Q. Wang, et al., Biomaterials 162 (2018) 47–59. doi: 10.1016/j.biomaterials.2018.01.042
37. [37]
  D. Chen, P. Zhang, M. Li, et al., Drug Deliv. 29 (2022) 574–587. doi: 10.1080/10717544.2022.2032874
38. [38]
  M. Tuttolomondo, S.T.D. Pham, M.G. Terp, et al., Mol. Ther. Nucleic. Acids 35 (2024) 102227. doi: 10.1016/j.omtn.2024.102227
39. [39]
  J. Lee, I. Sands, W. Zhang, L. Zhou, Y. Chen, Proc. Natl. Acad. Sci. U. S. A. 118 (2021) e2104511118. doi: 10.1073/pnas.2104511118
40. [40]
  S. Hyun, Y. Choi, H.N. Lee, et al., Chem. Sci. 9 (2018) 3820–3827. doi: 10.1039/c8sc00074c
41. [41]
  Y. Dang, Y. Feng, X. Chen, et al., Chin. Chem. Lett. 35 (2024) 109660. doi: 10.1016/j.cclet.2024.109660
42. [42]
  C. Li, J. Zhou, Y. Wu, et al., Nano Lett. 21 (2021) 3680–3689. doi: 10.1021/acs.nanolett.0c04468
43. [43]
  Y. Wu, W. Gu, J. Tang, Z.P. Xu, J. Mater. Chem. B 5 (2017) 7194–7203. doi: 10.1039/C7TB01635B
44. [44]
  C. Yu, K. Li, L. Xu, et al., Nano Res. 15 (2022) 9160–9168. doi: 10.1007/s12274-022-4573-2
45. [45]
  J. Wang, H. Ding, Y. Zhu, et al., Angew Chem. Int. Ed. 62 (2023) e202302255. doi: 10.1002/anie.202302255
46. [46]
  B. Hu, B. Li, K. Li, et al., Sci. Adv. 8 (2022) eabm1418. doi: 10.1126/sciadv.abm1418
47. [47]
  F. Joris, L. De Backer, T. Van de Vyver, et al., J. Control. Release 269 (2018) 266–276. doi: 10.1016/j.jconrel.2017.11.019
48. [48]
  E.J. Kwon, J.M. Bergen, S.H. Pun, Bioconjug. Chem. 19 (2008) 920–927. doi: 10.1021/bc700448h
49. [49]
  S. Ben Djemaa, K. Hervé-Aubert, L. Lajoie, et al., Biomacromolecules 20 (2019) 3076–3086. doi: 10.1021/acs.biomac.9b00637
50. [50]
  L. Zheng, S.R. Bandara, Z. Tan, C. Leal, Proc. Natl. Acad. Sci. U. S. A. 120 (2023) e2301067120. doi: 10.1073/pnas.2301067120
51. [51]
  X. Cao, X. Shang, Y. Guo, et al., Anal. Bioanal. Chem. 413 (2021) 3493–3499. doi: 10.1007/s00216-021-03297-5
52. [52]
  S. Oliveira, M.M. Fretz, A. Høgset, G. Storm, R.M. Schiffelers, Biochim. Biophys. Acta 1768 (2007) 1211–1217. doi: 10.1016/j.bbamem.2007.01.013
53. [53]
  J.A. Jørgensen, A.S. Longva, E. Hovig, S.L. Bøe, Nucleic Acid Ther. 23 (2013) 131–139. doi: 10.1089/nat.2012.0403
54. [54]
  Z. Zhang, M.K.G. Jayakumar, X. Zheng, et al., Nat. Commun. 10 (2019) 4586. doi: 10.1109/cvpr.2019.00472
55. [55]
  B. Mezghrani, L.M.A. Ali, S. Richeter, et al., ACS Appl. Mater. Interfaces 13 (2021) 29325–29339. doi: 10.1021/acsami.1c05848
56. [56]
  A. Puri, M. Viard, P. Zakrevsky, et al., Nanomedicine 26 (2020) 102176.
57. [57]
  Y. Yang, H. Ning, T. Xia, et al., Adv. Mater. 35 (2023) e2301409. doi: 10.1002/adma.202301409
58. [58]
  Y. Mo, M.H.Y. Cheng, A. D'Elia, K. Doran, et al., ACS Nano 17 (2023) 4688–4703. doi: 10.1021/acsnano.2c10936
59. [59]
  M.K. Jayakumar, A. Bansal, K. Huang, et al., ACS Nano 8 (2014) 4848–4858. doi: 10.1021/nn500777n
60. [60]
  J. Wang, L. Xie, T. Wang, et al., Acta Biomater. 59 (2017) 158–169. doi: 10.3901/JME.2017.08.158
61. [61]
  S. Roy, D. Zhu, W.J. Parak, N. Feliu, ACS Nano 14 (2020) 8012–8023. doi: 10.1021/acsnano.9b10219
62. [62]
  Y. Ma, M. Sha, S. Cheng, et al., Nanomaterials 8 (2018) 433. doi: 10.3390/nano8060433
63. [63]
  C. Wang, T. Zhao, Y. Li, et al., Adv. Drug Deliv. Rev. 113 (2017) 87–96.
64. [64]
  M. Wojnilowicz, A. Glab, A. Bertucci, F. Caruso, F. Cavalieri, ACS Nano 13 (2019) 187–202. doi: 10.1021/acsnano.8b05151
65. [65]
  Y.J. Choi, S.J. Kang, Y.J. Kim, Y.B. Lim, H.W. Chung, Drug Chem. Toxicol. 33 (2010) 357–366. doi: 10.3109/01480540903493507
66. [66]
  X. Xu, Z. Li, X. Zhao, L. Keen, X. Kong, Regen. Biomater. 3 (2016) 187–195. doi: 10.1093/rb/rbw010
67. [67]
  K. Dong, Z. Wang, Y. Zhang, J. Ren, X. Qu, ACS Appl. Mater. Interfaces 10 (2018) 31998–32005. doi: 10.1021/acsami.8b11972
68. [68]
  Y. Sun, Y. Sha, G. Cui, F. Meng, Z. Zhong, Adv. Drug Deliv. Rev. 192 (2023) 114624.
69. [69]
  E. Pandey, E.N. Harris, Mol. Ther. Nucleic Acids 33 (2023) 430–443.
70. [70]
  H. Du Rietz, H. Hedlund, S. Wilhelmson, P. Nordenfelt, A. Wittrup, Nat. Commun. 11 (2020) 1809.
71. [71]
  S.R. Bhattarai, E. Muthuswamy, A. Wani, et al., Pharm. Res. 27 (2010) 2556–2568. doi: 10.1007/s11095-010-0245-0
72. [72]
  M. Lu, H. Xing, A. Zheng, Y. Huang, X.J. Liang, Acc. Chem. Res. 56 (2023) 224–236. doi: 10.1021/acs.accounts.2c00464
73. [73]
  S. Liu, Q. Cheng, T. Wei, et al., Nat. Mater. 20 (2021) 701–710. doi: 10.1038/s41563-020-00886-0
74. [74]
  Q. Wang, Q. Jiang, D. Li, et al., Chin. Chem. Lett. 35 (2024) 108683.
75. [75]
  A. Debisschop, B. Bogaert, C. Muntean, S.C. De Smedt, K. Raemdonck, Curr. Opin. Chem. Biol. 83 (2024) 102531.
76. [76]
  A.K. Varkouhi, M. Scholte, G. Storm, H.J. Haisma, J. Control. Release 151 (2011) 220–228.
77. [77]
  E.E. Haywood, N.B. Handy, J.W. Lopez, M. Ho, B.A. Wilson, J. Biol. Chem. 297 (2021) 101347.
78. [78]
  A.K. Mondal, K. Lata, M. Singh, et al., Biochim. Biophys. Acta Biomembr. 1864 (2022) 184013.
79. [79]
  F.R. Ulhuq, G. Mariano, Microbiology 168 (2022) 001154.
80. [80]
  I. Plaza-Ga, V. Manzaneda-González, M. Kisovec, et al., J. Nanobiotechnology 17 (2019) 108.
81. [81]
  D.W. Schuerch, E.M. Wilson-Kubalek, R.K. Tweten, Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 12537–12542. doi: 10.1073/pnas.0500558102
82. [82]
  R.K. Tweten, E.M. Hotze, K.R. Wade, Annu. Rev. Microbiol. 69 (2015) 323–340. doi: 10.1146/annurev-micro-091014-104233
83. [83]
  A. Sáez-Cirión, S. Nir, M. Lorizate, et al., J. Biol. Chem. 277 (2002) 21776–21785.
84. [84]
  B.S. Joshi, M.A. de Beer, B.N.G. Giepmans, I.S. Zuhorn, ACS Nano 14 (2020) 4444–4455. doi: 10.1021/acsnano.9b10033
85. [85]
  X. Pei, X. Zhang, L. Zhang, et al., Chem. Eng. J. 421 (2021) 129774.
86. [86]
  A. Wittrup, A. Ai, X. Liu, et al., Nat. Biotechnol. 33 (2015) 870–876. doi: 10.1038/nbt.3298
87. [87]
  Z. Zhao, P. Qin, Y.W. Huang, Cell Calcium 94 (2021) 102360.
88. [88]
  Y. Wang, B. Jin, B. Li, et al., Int. J. Pharm. 623 (2022) 121890.
89. [89]
  D.J. Benton, S.J. Gamblin, P.B. Rosenthal, J.J. Skehel, Nature 583 (2020) 150–153. doi: 10.1038/s41586-020-2333-6
90. [90]
  Y. Xu, Y. Zheng, L. Wu, et al., ACS Appl. Mater. Interfaces 10 (2018) 9315–9324. doi: 10.1021/acsami.8b00507
91. [91]
  Y. Wan, P.M. Moyle, M.P. Christie, I. Toth, Nanomedicine 11 (2016) 907–919. doi: 10.2217/nnm.16.27
92. [92]
  L.M.A. Ali, M. Gary-Bobo, Cancers 14 (2022) 3597. doi: 10.3390/cancers14153597
93. [93]
  Y. Wang, L. Xiong, Z. Dong, et al., ACS Appl. Mater. Interfaces 15 (2023) 28941–28953. doi: 10.1021/acsami.3c03416
94. [94]
  C. Qiu, H.H. Han, J. Sun, et al., Nat. Commun. 10 (2019) 2702.
95. [95]
  J. Zhou, Z. Shao, J. Liu, et al., ACS Appl. Bio. Mater. 3 (2020) 2686–2701. doi: 10.1021/acsabm.9b01131
96. [96]
  M.M. Khan, N. Filipczak, V.P. Torchilin, J. Control. Release 330 (2021) 1220–1228.
97. [97]
  S.S. Ali Zaidi, F. Fatima, S.A. Ali Zaidi, et al., Nanobiotechnology 21 (2023) 381.
98. [98]
  R. Pan, W. Xu, Y. Ding, S. Lu, P. Chen, Mol. Pharm. 13 (2016) 1366–1374. doi: 10.1021/acs.molpharmaceut.6b00030
99. [99]
  A. Rydström, S. Deshayes, K. Konate, et al., PLoS One 6 (2011) e25924. doi: 10.1371/journal.pone.0025924
100. [100]
  K. Konate, A. Rydstrom, G. Divita, S. Deshayes, Curr. Pharm. Des. 19 (2013) 2869–2877. doi: 10.2174/1381612811319160004
101. [101]
  J. Ye, X. Pei, H. Cui, et al., J. Ind. Eng. Chem. 63 (2018) 103–111.
102. [102]
  Y. Xu, X. Zhang, N. Wang, et al., Int. J. Pharm. 584 (2020) 119469.
103. [103]
  M. Zorko, S. Jones, Ü. Langel, Adv. Drug Deliv. Rev. 180 (2022) 114044.
104. [104]
  A. Gori, G. Lodigiani, S.G. Colombarolli, G. Bergamaschi, A. Vitali, ChemMedChem 18 (2023) e202300236.
105. [105]
  C. Gupta, Y. Ren, B. Mertz, Biophys. J. 115 (2018) 2403–2412.
106. [106]
  S.Z. Hanz, N.S. Shu, J. Qian, et al., Angew Chem. Int. Ed. 55 (2016) 12376–12381. doi: 10.1002/anie.201605203
107. [107]
  Z. Zhao, C. Li, B. Song, et al., Biochem. Biophys. Res. Commun. 503 (2018) 1761–1767.
108. [108]
  S.M. Son, J. Yun, S.H. Lee, et al., Sci. Rep. 9 (2019) 11607.
109. [109]
  M.G. Damiano, R.K. Mutharasan, S. Tripathy, K.M. McMahon, C.S. Thaxton, Adv. Drug. Deliv. Rev. 65 (2013) 649–662.
110. [110]
  K.M. McMahon, C.S. Thaxton, Expert. Opin. Drug Deliv. 11 (2014) 231–247. doi: 10.1517/17425247.2014.866089
111. [111]
  A. Kontush, M. Lindahl, M. Lhomme, et al., Handb. Exp. Pharmacol. 224 (2015) 3–51. doi: 10.1007/978-3-319-09665-0_1
112. [112]
  R. Masimov, G. Büyükköroglu, Comb. Chem. High Throughput Screen. 26 ˘ (2023) 2541–2553. doi: 10.2174/1386207326666230406124524
113. [113]
  M. Yang, H. Jin, J. Chen, et al., Small 7 (2011) 568–573. doi: 10.1002/smll.201001589
114. [114]
  Y. Ding, Y. Wang, J. Zhou, et al., Biomaterials 35 (2014) 7214–7227.
115. [115]
  V.P. Torchilin, Nat. Rev. Drug Discov. 4 (2005) 145–160. doi: 10.1038/nrd1632
116. [116]
  B. Kim, S. Sun, J.A. Varner, et al., Adv. Mater. 31 (2019) e1902952.
117. [117]
  Y. Zhao, J. Qin, D. Yu, et al., Nat. Nanotechnol. 19 (2024) 1869–1879. doi: 10.1038/s41565-024-01769-0
118. [118]
  L. Wang, G. Wang, W. Mao, et al., Nat. Commun. 14 (2023) 3366.
119. [119]
  Y. Zhuo, Z. Luo, Z. Zhu, et al., Nat. Nanotechnol. 19 (2024) 1858–1868. doi: 10.1038/s41565-024-01785-0
120. [120]
  W. Tai, J. Control. Release 307 (2019) 98–107.
121. [121]
  W. Tai, X. Gao, Biomaterials 178 (2018) 720–727.
122. [122]
  A. Serrano-Puebla, P. Boya, Ann. N Y Acad. Sci. 1371 (2016) 30–44. doi: 10.1111/nyas.12966
123. [123]
  S.F. Dowdy, R.L. Setten, X.S. Cui, S.G. Jadhav, Nucleic Acid Ther. 32 (2022) 361–368. doi: 10.1089/nat.2022.0004
124. [124]
  M.A. Beach, S.L.Y. Teo, M.Z. Chen, et al., ACS Appl. Mater. Interfaces 14 (2022) 3653–3661. doi: 10.1021/acsami.1c18359
1. [1]
  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
2. [2]
  Yunjie Dang , Yanru Feng , Xiao Chen , Chaoxing He , Shujie Wei , Dingyang Liu , Jinlong Qi , Huaxing Zhang , Shaokun Yang , Zhiyun Niu , Bai Xiang . Development of a multi-level pH-responsive lipid nanoplatform for efficient co-delivery of siRNA and small-molecule drugs in tumor treatment. Chinese Chemical Letters, 2024, 35(12): 109660-. doi: 10.1016/j.cclet.2024.109660
3. [3]
  Mengmeng Yuan , Xiwen Hu , Na Li , Limin Xu , Mengxi Zhu , Xing Pei , Rui Li , Lu Sun , Yupeng Chen , Fei Yu , Huining He . Kidney targeted delivery of siRNA mediated by peptide-siRNA conjugate for the treatment of acute kidney injury. Chinese Chemical Letters, 2025, 36(6): 110251-. doi: 10.1016/j.cclet.2024.110251
4. [4]
  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. Chinese Chemical Letters, 2025, 36(3): 110228-. doi: 10.1016/j.cclet.2024.110228
5. [5]
  Kunya Wang , Bingyu Liu , Daojiang Yan , Jian Bai , Haibo Yu , Youcai Hu . Full biosynthetic pathway of pyrrolobenzoxazines. Chinese Chemical Letters, 2025, 36(1): 109811-. doi: 10.1016/j.cclet.2024.109811
6. [6]
  Jindian Duan , Xiaojuan Ding , Pui Ying Choy , Binyan Xu , Luchao Li , Hong Qin , Zheng Fang , Fuk Yee Kwong , Kai Guo . Oxidative spirolactonisation for modular access of γ-spirolactones via a radical tandem annulation pathway. Chinese Chemical Letters, 2024, 35(10): 109565-. doi: 10.1016/j.cclet.2024.109565
7. [7]
  Huaran Zhang , Yuting Huang , Yingjie Tang , Dekun Kong , Yi Zou . Genome mining of multi-substituted alkylresorcinols from a hybrid highly reducing- and type Ⅲ- polyketide pathway. Chinese Chemical Letters, 2024, 35(7): 108968-. doi: 10.1016/j.cclet.2023.108968
8. [8]
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沈阳化工大学材料科学与工程学院沈阳 110142