Citation: Jingjing Li, Juanjuan Wei, Yixuan Gao, Qi Zhao, Jianghui Sun, Jin Ouyang, Na Na. Peptide-assembled siRNA nanomicelles confine MnO_x-loaded silicages for synergistic chemical and gene-regulated cancer therapy[J]. Chinese Chemical Letters, ;2023, 34(4): 107662. doi: 10.1016/j.cclet.2022.07.005 shu

Peptide-assembled siRNA nanomicelles confine MnO_x-loaded silicages for synergistic chemical and gene-regulated cancer therapy

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100085, China

nana@bnu.edu.cn

Received Date: 30 March 2022
Revised Date: 16 June 2022
Accepted Date: 6 July 2022
Available Online: 8 July 2022

Figures(5)

Chemodynamic therapy (CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria (the main site of intracellular ROS production). Herein, to obtain a multimodal strategy, peptide-assembled siRNA nanomicelles were prepared to confine ultrasmall MnO in small silica cages (silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall MnO, MnO-inside-loaded silicages (10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of siRNA and MnO-loaded silicages were employed to obtain silicage@MnO-siRNA nanomicelles (SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of siRNA and mitochondria-targeted delivery of MnO-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.
- Peptide-assembled siRNA nanomicelles,
- MnO_x-loaded silicages,
- GSH-stimulated release,
- Mitochondria-targeted delivery,
- Cancer therapy
1. [1]
  S.E. Weinberg, N.S. Chandel, Nat. Chem. Biol. 11 (2015) 9–15. doi: 10.1038/nchembio.1712
2. [2]
  L.A. Sena, N.S. Chandel, Mol. Cell 48 (2012) 158–167. doi: 10.1016/j.molcel.2012.09.025
3. [3]
  G.S. Shadel, T.L. Horvath, Cell 163 (2015) 560–569. doi: 10.1016/j.cell.2015.10.001
4. [4]
  P.H.G.M. Willems, R. Rossignol, C.E.J. Dieteren, M.P. Murphy, W.J.H. Koopman, Cell Metab. 22 (2015) 207–218. doi: 10.1016/j.cmet.2015.06.006
5. [5]
  S.S. Sabharwal, P.T. Schumacker, Nat. Rev. Cancer 14 (2014) 709–721. doi: 10.1038/nrc3803
6. [6]
  B.C. Dickinson, C.J. Chang, Nat. Chem. Biol. 7 (2011) 504–511. doi: 10.1038/nchembio.607
7. [7]
  F. Jiang, C. Yang, B. Ding, et al., Chin. Chem. Lett. 33 (2022) 2959–2964. doi: 10.1016/j.cclet.2021.12.096
8. [8]
  N. Gong, X. Ma, X. Ye, et al., Nat. Nanotechnol. 14 (2019) 379–387. doi: 10.1038/s41565-019-0373-6
9. [9]
  X. Hu, F. Li, F. Xia, et al., J. Am. Chem. Soc. 142 (2020) 1636–1644. doi: 10.1021/jacs.9b13586
10. [10]
  B. Ma, S. Wang, F. Liu, et al., J. Am. Chem. Soc. 141 (2019) 849–857. doi: 10.1021/jacs.8b08714
11. [11]
  S. Wang, G. Yu, Z. Wang, et al., Angew. Chem. Int. Ed. 58 (2019) 14758–14763. doi: 10.1002/anie.201908997
12. [12]
  X. Li, R. Luo, X. Liang, Q. Wu, C. Gong, Chin. Chem. Lett. 33 (2022) 2213–2230. doi: 10.1016/j.cclet.2021.11.048
13. [13]
  Y. Liu, X. Ji, W.W.L. Tong, et al., Angew. Chem. Int. Ed. 57 (2018) 1510–1513. doi: 10.1002/anie.201710144
14. [14]
  M. Ye, Y. Gao, M. Liang, et al., Chin. Chem. Lett. 33 (2022) 4197–4202. doi: 10.1016/j.cclet.2022.01.086
15. [15]
  Z. Dong, L. Feng, Y. Chao, et al., Nano Lett. 19 (2019) 805–815. doi: 10.1021/acs.nanolett.8b03905
16. [16]
  N. Chen, W. Fu, J. Zhou, et al., Chin. Chem. Lett. 32 (2021) 2405–2410. doi: 10.1016/j.cclet.2021.02.030
17. [17]
  L.S. Lin, J. Song, L. Song, et al., Angew. Chem. Int. Ed. 57 (2018) 4902–4906. doi: 10.1002/anie.201712027
18. [18]
  Y. Wang, C. Zhang, H. Zhang, L. Feng, L. Liu, Chin. Chem. Lett. 33 (2022) 4605–4609. doi: 10.1016/j.cclet.2022.03.076
19. [19]
  W. Xuan, Y. Xia, T. Li, et al., J. Am. Chem. Soc. 142 (2020) 937–944. doi: 10.1021/jacs.9b10755
20. [20]
  Z. Cao, L. Zhang, K. Liang, et al., Adv. Sci. 5 (2018) 1801155. doi: 10.1002/advs.201801155
21. [21]
  C. Liu, D. Wang, S. Zhang, et al., ACS Nano 13 (2019) 4267–4277. doi: 10.1021/acsnano.8b09387
22. [22]
  P. Yu, X. Li, G. Cheng, et al., Chin. Chem. Lett. 32 (2021) 2127–2138. doi: 10.1016/j.cclet.2021.02.015
23. [23]
  L. Lin, S. Wang, H. Deng, et al., J. Am. Chem. Soc. 142 (2020) 15320–15330. doi: 10.1021/jacs.0c05604
24. [24]
  L. Shi, Y. Wang, C. Zhang, et al., Angew. Chem. Int. Ed. 60 (2021) 9562–9572. doi: 10.1002/anie.202014415
25. [25]
  X. Chen, Y. Chen, C. Wang, et al., Angew. Chem. Int. Ed. 60 (2021) 21905–21910. doi: 10.1002/anie.202107588
26. [26]
  C. Liu, Y. Cao, Y. Cheng, et al., Nat. Commun. 11 (2020) 1735. doi: 10.1038/s41467-020-15591-4
27. [27]
  W. Zhen, Y. Liu, W. Wang, et al., Angew. Chem. Int. Ed. 59 (2020) 9491–9497. doi: 10.1002/anie.201916142
28. [28]
  X. Zhao, K. Guo, K. Zhang, et al., Adv. Mater. 34 (2022) 2108263. doi: 10.1002/adma.202108263
29. [29]
  Y. Wang, Y. Li, Z. Zhang, et al., Adv. Mater. 33 (2021) 2103748. doi: 10.1002/adma.202103748
30. [30]
  Y. Wang, Y. Song, G. Zhu, D. Zhang, X. Liu, Chin. Chem. Lett. 29 (2018) 1685–1688. doi: 10.1016/j.cclet.2017.12.004
31. [31]
  N.P. Aditya, S. Aditya, H. Yang, et al., Food Chem. 173 (2015) 7–13. doi: 10.1016/j.foodchem.2014.09.131
32. [32]
  K. Ma, Y. Gong, T. Aubert, et al., Nature 558 (2018) 577–580. doi: 10.1038/s41586-018-0221-0
33. [33]
  R. Zandi, D. Reguera, R.F. Bruinsma, W.M. Gelbart, J. Rudnick, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 15556. doi: 10.1073/pnas.0405844101
34. [34]
  Y. Yang, T.L. Willis, R.W. Button, et al., Nat. Commun. 10 (2019) 3759. doi: 10.1038/s41467-019-11671-2
35. [35]
  S.V. Patwardhan, F.S. Emami, R.J. Berry, et al., J. Am. Chem. Soc. 134 (2012) 6244–6256. doi: 10.1021/ja211307u
36. [36]
  K. Nagy-Smith, E. Moore, J. Schneider, R. Tycko, Proc. Natl. Acad. Sci. U. S. A. 112 (2015) 9816. doi: 10.1073/pnas.1509313112
37. [37]
  S. Guan, A. Munder, S. Hedtfeld, et al., Nat. Nanotechnol. 14 (2019) 287–297. doi: 10.1038/s41565-018-0358-x
38. [38]
  J. Sun, X. Cai, C. Wang, et al., J. Am. Chem. Soc. 143 (2021) 868–878. doi: 10.1021/jacs.0c10517
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4. [4]
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6. [6]
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7. [7]
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8. [8]
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11. [11]
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15. [15]
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18. [18]
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Peptide-assembled siRNA nanomicelles confine MnOx-loaded silicages for synergistic chemical and gene-regulated cancer therapy

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通讯作者: 陈斌, bchen63@163.com

Peptide-assembled siRNA nanomicelles confine MnO_x-loaded silicages for synergistic chemical and gene-regulated cancer therapy