Intelligent Nano‐Cage for Precision Delivery of CRISPR‐Cas9 and ACC Inhibitors to Enhance Antitumor Cascade Therapy Through Lipid Metabolism Disruption

Wei Zhao; La Zhang; Jiao Guo; Qing Xu; Mi Zhang; Hongqing Liu; Cong Ren; Yifan Zhao; Jianwei Wang; Qiling Peng; Ning Jiang

doi:10.1002/adfm.202418090

journal article·2025-03Open access

Intelligent Nano‐Cage for Precision Delivery of CRISPR‐Cas9 and ACC Inhibitors to Enhance Antitumor Cascade Therapy Through Lipid Metabolism Disruption

Wei Zhao, La Zhang, Jiao Guo, Qing Xu, Mi Zhang, Hongqing Liu, Cong Ren, Yifan Zhao, Jianwei Wang, Qiling Peng, Ning Jiang

Advanced Functional Materials· Volume 35· Issue 13

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Source abstract

Abstract

Abstract Reprogramming in lipid metabolism is a hallmark of cancer, and targeting the pivotal enzyme in fatty acid synthesis, acetyl‐CoA carboxylase 1 (ACC1), presents a promising therapeutic strategy. Herein, a nano‐cage encapsulated is constructed by peptide‐modified erythrocyte membrane (NTA630‐NCs‐RBCM‐T) for delivering CRISPR‐Cas9 and ACC1 inhibitors to enable dual‐layer inhibition of ACC1, thereby optimizing the effectiveness of antitumor cascade therapy. NTA630‐NCs‐RBCM‐T are efficiently delivered to cancer cells via peptide‐mediated targeting, releasing Cas9 complexes and ND630 in response to lysosomal enzymes, proton sponge effects, and elevated glutathione levels. The concurrent inhibition of fatty acid synthesis pathways, achieved by Cas9‐mediated ubiquitin‐specific protease 22 (USP22) knockdown and direct inhibition by ND630, enhances polyunsaturated fatty acids (PUFAs) uptake, triggers lipid peroxidation, leading to tumor cell death, particularly ferroptosis, and apoptosis, resulting in effective anti‐tumor activity.

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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced biosensing and bioanalysis techniques · Protein Degradation and Inhibitors

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

College of Basic Medical Sciences Chongqing Medical University Chongqing 400016 China

Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Chongqing Medical University Chongqing 400016 China

Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China

Department of Bioinformatics Chongqing Medical University Chongqing 400016 China

Department of Medicinal Chemistry College of Pharmacy Chongqing Medical University Chongqing 400016 China

Department of Pathology College of Basic Medical Sciences Chongqing Medical University Chongqing 400016 China

Molecular Medicine Diagnostic and Testing Center Chongqing Medical University Chongqing 400016 China

Department of Pathology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China

Funding

National Natural Science Foundation of China

References (50)

Show source-provided references

1. 10.3322/caac.2166010.3322/caac.21660 ↗

2. 10.1126/scitranslmed.aat780710.1126/scitranslmed.aat7807 ↗

3. 10.1038/nrc.2016.8910.1038/nrc.2016.89 ↗

4. 10.1016/j.cmet.2019.11.01010.1016/j.cmet.2019.11.010 ↗

5. 10.1007/s10863-020-09846-410.1007/s10863-020-09846-4 ↗

6. 10.1016/j.pharmthera.2018.07.00610.1016/j.pharmthera.2018.07.006 ↗

7. 10.3390/ijms23231526310.3390/ijms232315263 ↗

8. 10.1016/j.cmet.2017.08.00210.1016/j.cmet.2017.08.002 ↗

9. 10.1186/s13068-020-01767-z10.1186/s13068-020-01767-z ↗

10. 10.1126/sciadv.adi246510.1126/sciadv.adi2465 ↗

11. 10.1038/nm.418110.1038/nm.4181 ↗

12. 10.1073/pnas.152068611310.1073/pnas.1520686113 ↗

13. 10.1016/j.cmet.2013.05.01710.1016/j.cmet.2013.05.017 ↗

14. 10.1038/s41467-022-29846-910.1038/s41467-022-29846-9 ↗

15. 10.1038/s41392-019-0089-y10.1038/s41392-019-0089-y ↗

16. 10.1038/natrevmats.2016.1410.1038/natrevmats.2016.14 ↗

17. 10.1021/acsnano.3c1126010.1021/acsnano.3c11260 ↗

18. 10.1126/science.122956810.1126/science.1229568 ↗

19. 10.1002/advs.20190017210.1002/advs.201900172 ↗

20. 10.1016/j.jconrel.2023.02.03610.1016/j.jconrel.2023.02.036 ↗

21. 10.1126/sciadv.abn738210.1126/sciadv.abn7382 ↗

22. 10.1146/annurev-physiol-012110-14231710.1146/annurev-physiol-012110-142317 ↗

23. 10.1038/nature0690710.1038/nature06907 ↗

24. 10.1038/nature2516410.1038/nature25164 ↗

25. 10.1021/nl502044x10.1021/nl502044x ↗

26. 10.1158/0008-5472.CAN-09-387110.1158/0008-5472.CAN-09-3871 ↗

27. 10.1016/j.cmet.2022.09.02310.1016/j.cmet.2022.09.023 ↗

28. 10.1126/sciadv.abb400510.1126/sciadv.abb4005 ↗

29. 10.1021/ja508802410.1021/ja5088024 ↗

30. 10.1073/pnas.110663410810.1073/pnas.1106634108 ↗

31. 10.1002/adhm.20220096210.1002/adhm.202200962 ↗

32. 10.1021/acsnano.8b0520010.1021/acsnano.8b05200 ↗

33. 10.1039/c3nr03064d10.1039/c3nr03064d ↗

34. 10.1002/adfm.20150105010.1002/adfm.201501050 ↗

35. 10.1021/acsnano.2c1083010.1021/acsnano.2c10830 ↗

36. 10.3390/microorganisms904079010.3390/microorganisms9040790 ↗

37. 10.1016/j.tcb.2015.10.01410.1016/j.tcb.2015.10.014 ↗

38. 10.3389/fphys.2019.0013910.3389/fphys.2019.00139 ↗

39. 10.1038/s41392-022-01004-z10.1038/s41392-022-01004-z ↗

40. 10.1016/j.cellsig.2024.11125810.1016/j.cellsig.2024.111258 ↗

41. 10.1016/j.freeradbiomed.2018.09.04310.1016/j.freeradbiomed.2018.09.043 ↗

42. 10.1016/j.cell.2013.12.01010.1016/j.cell.2013.12.010 ↗

43. 10.1073/pnas.141551811110.1073/pnas.1415518111 ↗

44. 10.1016/j.freeradbiomed.2018.09.01410.1016/j.freeradbiomed.2018.09.014 ↗

45. 10.1038/cdd.2015.15810.1038/cdd.2015.158 ↗

46. 10.1038/s41467-021-20904-210.1038/s41467-021-20904-2 ↗

47. 10.1016/j.bbrc.2016.10.06810.1016/j.bbrc.2016.10.068 ↗

48. 10.1073/pnas.160324411310.1073/pnas.1603244113 ↗

49. 10.1016/j.biomaterials.2022.12156510.1016/j.biomaterials.2022.121565 ↗

50. 10.1038/s41573-021-00339-610.1038/s41573-021-00339-6 ↗