Citation: Qiu Wang, Qikun Jiang, Dan Li, Zimeng Yang, Lin Gao, Fan Liu, Chang Li, Yao Feng, Zhonggui He, Cong Luo, Jin Sun. Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury[J]. Chinese Chemical Letters, ;2024, 35(2): 108683. doi: 10.1016/j.cclet.2023.108683 shu

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

Qiu Wang ^{a, 1} ,
Qikun Jiang ^{a, 1} ,
Dan Li ^a ,
Zimeng Yang ^a ,
Lin Gao ^a ,
Fan Liu ^a ,
Chang Li ^a ,
Yao Feng ^b ,
Zhonggui He ^a ,
Cong Luo ^{a, *,} ,
Jin Sun ^{a, *,}

a.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
Kangya of Ningxia Pharmaceutical Co. Ltd., Yinchuan 750000, China

luocong@syphu.edu.cn

sunjin@syphu.edu.cn

Received Date: 2 March 2023
Revised Date: 7 June 2023
Accepted Date: 11 June 2023
Available Online: 17 June 2023

Figures(6)

Small interfering RNA (siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases. Nevertheless, the effective delivery of siRNA to desired destination still remains challenging due to poor stability, high molecular weight and negative charge. Currently, ionizable lipid nanoparticle (LNP) has been extensively used as vector for effective delivery of siRNA. Herein, we report a mannose-modified LNP (M-MC3 LNP@TNFα) loading tumor necrosis factor α (TNFα) siRNA for targeting liver macrophages, achieving effectively inhibit acute liver injury. The M-MC3 LNP@TNFα not only increases the internalization of LNP by macrophages, but also enhances the gene silencing efficiency of TNFα in vitro. Additionally, the M-MC3 LNP@TNFα exhibits higher accumulation in liver of healthy mice than that of MC3 LNP@TNFα (un-modified LNP) owing to the targeting effect of mannose. As expected, the M-MC3 LNP@TNFα significantly suppresses the expression of TNFα and ameliorates liver damage in acute liver injury model. Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.
- Lipid nanoparticle,
- Targeting siRNA delivery,
- Acute liver injury,
- Gene silencing,
- Tumor necrosis factor α
1. [1]
  F. Ding, H. Zhang, Q. Li, et al., J. Mater. Chem. B 9 (2021) 5136. doi: 10.1039/d1tb00736j
2. [2]
  Q. Yin, X. Song, P. Yang, et al., Nanomedicine 48 (2023) 102649. doi: 10.1016/j.nano.2022.102649
3. [3]
  H. He, N. Zheng, Z. Song, et al., ACS Nano 10 (2016) 1859–1870. doi: 10.1021/acsnano.5b05470
4. [4]
  S. Chu, C. Tang, C. Yin, Biomaterials 52 (2015) 229–239. doi: 10.1016/j.biomaterials.2015.02.044
5. [5]
  P. Patel, J. Fetse, C. Lin, et al., Acta Biomater 154 (2022) 374–384. doi: 10.1016/j.actbio.2022.09.065
6. [6]
  M. Kim, M. Jeong, S. Hur, et al., Sci. Adv. 7 (2021) eabf4398. doi: 10.1126/sciadv.abf4398
7. [7]
  C. He, L. Yin, C. Tang, et al., Biomaterials 34 (2013) 2843–2854. doi: 10.1016/j.biomaterials.2013.01.033
8. [8]
  K. Li, M. Lu, X. Xia, et al., Chin. Chem. Lett. 32 (2021) 1010–1016. doi: 10.1016/j.cclet.2020.09.010
9. [9]
  J. Zhou, L. Sun, L. Liu, et al., J. Control. Release 343 (2022) 175–186. doi: 10.1016/j.jconrel.2022.01.038
10. [10]
  H. Zhang, F. Ding, Z. Zhu, et al., Int. J. Pharm. 631 (2023) 122489. doi: 10.1016/j.ijpharm.2022.122489
11. [11]
  B. Hu, B. Li, K. Li, et al., Sci. Adv. 8 (2022) eabm1418. doi: 10.1126/sciadv.abm1418
12. [12]
  S. Liu, J. Liu, H. Li, et al., Biomaterials 287 (2022) 121645. doi: 10.1016/j.biomaterials.2022.121645
13. [13]
  D. Yin, M. Zhang, J. Chen, et al., Chin. Chem. Lett. 32 (2021) 1731–1736. doi: 10.1016/j.cclet.2020.12.005
14. [14]
  H. Tanaka, Y. Sakurai, J. Anindita, et al., Adv. Drug Deliv. Rev. 154 (2020) 210–226.
15. [15]
  S. Dilliard, D. Siegwart, Nat. Rev. Mater. 8 (2023) 282–300. doi: 10.1038/s41578-022-00529-7
16. [16]
  Y. Wang, C. Li, L. Du, et al., Chin. Chem. Lett. 31 (2020) 275–280. doi: 10.1016/j.cclet.2019.03.040
17. [17]
  C. Ma, D. Zhu, W. Lin, et al., Chem. Commun. 58 (2022) 4168. doi: 10.1039/d1cc06655b
18. [18]
  S. Guo, B. Liu, M. Zhang, et al., Chin. Chem. Lett. 32 (2021) 102–106. doi: 10.1016/j.cclet.2020.11.024
19. [19]
  H. Kim, A. Kim, K. Miyata, et al., Adv. Drug Deliv. Rev. 104 (2016) 61–67. doi: 10.1016/j.addr.2016.06.011
20. [20]
  N. Dammes, D. Peer, Trends Pharmacol. Sci. 41 (2020) 755–775. doi: 10.1016/j.tips.2020.08.004
21. [21]
  J. Ma, J. Zhang, L. Chi, et al., Chin. Chem. Lett. 31 (2020) 1427–1431. doi: 10.1016/j.cclet.2020.02.034
22. [22]
  S. Yonezawa, H. Koide, T. Asai, Adv. Drug Deliv. Rev. 154 (2020) 64–78. doi: 10.1016/j.addr.2020.07.022
23. [23]
  Q. Wang, Z. Wang, X. Sun, et al., J. Control. Release 351 (2022) 102–122. doi: 10.1016/j.jconrel.2022.09.015
24. [24]
  S. Liu, Q. Cheng, Tuo. Wei, et al., Nat. Mater. 20 (2021) 701–710. doi: 10.1038/s41563-020-00886-0
25. [25]
  A. Akinc, M. Maier, M. Manoharan, et al., Nat. Nanotechnol. 14 (2019) 1084–1087. doi: 10.1038/s41565-019-0591-y
26. [26]
  V. Apostolopoulos, T. Thalhammer, A. Tzakos, et al., J. Drug Deliv. 2013 (2013) 869718.
27. [27]
  H. Xiong, S. Liu, T. Wei, et al., J. Control. Release 325 (2020) 198–205. doi: 10.1016/j.jconrel.2020.06.030
28. [28]
  J. Kang, D. Kim, J. Choi, et al., Food Chem. Toxicol. 57 (2013) 132–139. doi: 10.1016/j.fct.2013.03.016
29. [29]
  G.L. Su, Am. J. Physiol. Gastrointest. Liver Physiol. 283 (2002) G256–G265. doi: 10.1152/ajpgi.00550.2001
30. [30]
  Y. Ding, S. Zhang, Z. Sun, et al. Acta Biomater. 146 (2022) 385–395. doi: 10.1016/j.actbio.2022.04.021
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2. [2]
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4. [4]
  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
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7. [7]
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  Xing Tian , Di Wu , Wanheng Wei , Guifu Dai , Zhanxian Li , Benhua Wang , Mingming Yu . A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death, inflammation and fatty liver tissue. Chinese Chemical Letters, 2024, 35(6): 108912-. doi: 10.1016/j.cclet.2023.108912
9. [9]
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10. [10]
  Dandan Tang , Ningge Xu , Yuyang Fu , Wei Peng , Jinsheng Wu , Heng Liu , Fabiao Yu . Rationally designed an innovative proximity labeling near-infrared fluorogenic probe for imaging of peroxynitrite in acute lung injury. Chinese Chemical Letters, 2025, 36(5): 110082-. doi: 10.1016/j.cclet.2024.110082
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  Han-Min Wang , Yan-Chen Li , Lu-Lu Sun , Ming-Ye Tang , Jia Liu , Jiahao Cai , Lei Dong , Jia Li , Yi Zang , Hai-Hao Han , Xiao-Peng He . Protein-encapsulated long-wavelength fluorescent probe hybrid for imaging lipid droplets in living cells and mice with non-alcoholic fatty liver. Chinese Chemical Letters, 2024, 35(11): 109603-. doi: 10.1016/j.cclet.2024.109603
12. [12]
  Botao QU , Qian WANG , Xiaogang NING , Yuxin ZHOU , Ruiping ZHANG . Deeply penetrating photoacoustic imaging in tumor tissues based on dual-targeted melanin nanoparticle. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 1025-1032. doi: 10.11862/CJIC.20230416
13. [13]
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17. [17]
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18. [18]
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