journal article·2025-11-12

Magnetically Driven High-Speed Rolling Nanoclusters for Enhanced CRISPR/Cas9 Genome Editing

Huating Kong, Xia Liu, Kai Xia, Yong Guan, Jichao Zhang, Yu Zhang, Bingxin Liu, Zhilei Ge, Qian Li, Xiaolei Zuo, Lihua Wang, Jiang Li, Ying Zhu, Chunhai Fan

ACS Applied Materials & Interfaces· Volume 17· Issue 45
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Abstract

Despite the tremendous potential of the CRISPR/Cas9 gene-editing technology in precision therapeutics, intracellular delivery remains a major challenge. High cytoplasmic viscosity and lysosomal entrapment significantly impair the cytosolic transport and gene-editing efficiency. In this study, we demonstrate that both the size and magnetic responsiveness of Fe 3 O 4 nanoclusters can be finely tuned by modulating ionic strength, enabling their rapid propulsion under external magnetic fields. Leveraging this property, we develop magnetic nanoparticle cluster nanorobots (MagCbots) of approximately 200 nm in size by electrostatically assembling Fe 3 O 4 nanoclusters with CRISPR-Cas9 plasmids. Under magnetic actuation, MagCbots exhibit rapid rotation in highly viscous intracellular environments, achieving a linear velocity of ∼0.41 μm/s. MagCbots reduce intracellular viscosity by approximately 50% and enhance lysosomal escape efficiency by 3-fold compared to nonactuated counterparts. Their porous architecture not only offers high payload capacity but also protects plasmid DNA from enzymatic degradation. Notably, MagCbots enable efficient genome editing of both PD1 and PLK1 genes across various cell lines including hard-to-transfect Jurkat T cells. This magnetically driven nanorobot platform presents a promising strategy for active intracellular delivery and holds significant potential for advancing gene therapy and related biomedical applications.
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Research context

OpenAlex topics: Micro and Nano Robotics · Advanced Nanomaterials in Catalysis · Advanced biosensing and bioanalysis techniques

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

Affiliations

Institute of Materiobiology, College of Sciences

Shanghai University

The Interdisciplinary Research Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute

Chinese Academy of Sciences

Department of Stomatology, Xinhua Hospital, School of Medicine

Shanghai Jiao Tong University

Jiaxing Key Laboratory of Biosemiconductors

Xiangfu Laboratory

National Synchrotron Radiation Laboratory

University of Science and Technology of China

State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine

Funding

Natural Science Foundation of Shanghai Municipality · National Key Research and Development Program of China · National Natural Science Foundation of China · New Cornerstone Investigator Program · Xiangfu Lab Research Project · Shanghai ?Science and Technology Innovation Action Plan? Fundamental Research Project · Shanghai Science and Technology Development Funds

References (61)

Show source-provided references
1. 10.1038/s41565-024-01851-710.1038/s41565-024-01851-7 ↗
2. 10.1038/s41578-024-00725-710.1038/s41578-024-00725-7 ↗
3. 10.1002/smll.20230943110.1002/smll.202309431 ↗
4. 10.1021/acs.chemrev.3c0055010.1021/acs.chemrev.3c00550 ↗
5. 10.1038/s41467-024-46447-w10.1038/s41467-024-46447-w ↗
6. 10.1038/nrg376310.1038/nrg3763 ↗
7. 10.1038/nmeth.399310.1038/nmeth.3993 ↗
8. 10.1016/j.mattod.2018.12.00310.1016/j.mattod.2018.12.003 ↗
9. 10.1002/advs.20190338110.1002/advs.201903381 ↗
10. 10.1039/C7NR07999K10.1039/C7NR07999K ↗
11. 10.1002/anie.20150603010.1002/anie.201506030 ↗
12. 10.1038/s41551-017-0137-210.1038/s41551-017-0137-2 ↗
13. 10.1016/S0006-3495(87)83244-710.1016/S0006-3495(87)83244-7 ↗
14. 10.1016/j.chempr.2019.05.02310.1016/j.chempr.2019.05.023 ↗
15. 10.1146/annurev.biophys.37.032807.12582410.1146/annurev.biophys.37.032807.125824 ↗
16. 10.1002/adma.20170197010.1002/adma.201701970 ↗
17. 10.1021/acsnano.3c0194210.1021/acsnano.3c01942 ↗
18. 10.1038/s41467-024-49217-w10.1038/s41467-024-49217-w ↗
19. 10.1038/s41565-023-01577-y10.1038/s41565-023-01577-y ↗
20. 10.1002/advs.20231021110.1002/advs.202310211 ↗
21. 10.1002/anie.20170327610.1002/anie.201703276 ↗
22. 10.1039/C9CC07250K10.1039/C9CC07250K ↗
23. 10.1016/j.nanoms.2024.05.01310.1016/j.nanoms.2024.05.013 ↗
24. 10.1038/s41570-021-00281-610.1038/s41570-021-00281-6 ↗
25. 10.1002/anie.20180675910.1002/anie.201806759 ↗
26. 10.1039/C9CS00090A10.1039/C9CS00090A ↗
27. 10.1021/acsnano.6b0141510.1021/acsnano.6b01415 ↗
28. 10.1002/anie.20200374810.1002/anie.202003748 ↗
29. 10.1038/s41565-023-01527-810.1038/s41565-023-01527-8 ↗
30. 10.1126/sciadv.aay441210.1126/sciadv.aay4412 ↗
31. 10.1002/adma.20160545810.1002/adma.201605458 ↗
32. 10.1126/scirobotics.aaz951910.1126/scirobotics.aaz9519 ↗
33. 10.1186/s12951-016-0219-410.1186/s12951-016-0219-4 ↗
34. 10.1186/s12951-019-0440-z10.1186/s12951-019-0440-z ↗
35. 10.1038/nnano.2008.3010.1038/nnano.2008.30 ↗
36. 10.1002/adma.20070318110.1002/adma.200703181 ↗
37. 10.1039/c5ra07278f10.1039/c5ra07278f ↗
38. 10.1021/ja048605910.1021/ja0486059 ↗
39. 10.1038/nprot.2013.14310.1038/nprot.2013.143 ↗
40. 10.1002/anie.20170657010.1002/anie.201706570 ↗
41. 10.1038/s41565-021-00858-810.1038/s41565-021-00858-8 ↗
42. 10.1039/D0CS01127D10.1039/D0CS01127D ↗
43. 10.1021/cr900267p10.1021/cr900267p ↗
44. 10.1039/C6CC09916E10.1039/C6CC09916E ↗
45. 10.1364/OE.18.01660710.1364/OE.18.016607 ↗
46. 10.1103/PhysRevLett.103.14810110.1103/PhysRevLett.103.148101 ↗
47. 10.1021/ja409686x10.1021/ja409686x ↗
48. 10.1039/C6NR00859C10.1039/C6NR00859C ↗
49. 10.1126/sciadv.abb400510.1126/sciadv.abb4005 ↗
50. 10.1021/acsnano.0c0859610.1021/acsnano.0c08596 ↗
51. 10.1002/advs.20230061410.1002/advs.202300614 ↗
52. 10.1002/adma.20150623210.1002/adma.201506232 ↗
53. 10.1021/ja209351u10.1021/ja209351u ↗
54. 10.1021/nn305030g10.1021/nn305030g ↗
55. 10.1002/anie.20170388610.1002/anie.201703886 ↗
56. 10.1126/science.aaa134810.1126/science.aaa1348 ↗
57. 10.1038/nature1395410.1038/nature13954 ↗
58. 10.1002/anie.20060429510.1002/anie.200604295 ↗
59. 10.1038/nm72510.1038/nm725 ↗
60. 10.1021/acs.chemrev.6b0079910.1021/acs.chemrev.6b00799 ↗
61. 10.1371/journal.pone.010288610.1371/journal.pone.0102886 ↗