journal article·2023-01

Disturbed Flow‐Facilitated Margination and Targeting of Nanodisks Protect against Atherosclerosis

Chuan‐Rong Zhao, Jingyi Li, Zhi‐Tong Jiang, Juan‐Juan Zhu, Jia‐Nan Zhao, Qian‐Ru Yang, Weijuan Yao, Wei Pang, Ning Li, Miaorong Yu, Yong Gan, Jing Zhou

Small· Volume 19· Issue 2
Publisher page

Abstract

Abstract Disturbed blood flow induces endothelial pro‐inflammatory responses that promote atherogenesis. Nanoparticle‐based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical‐step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk‐shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro‐atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk‐shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk‐shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti‐inflammatory and anti‐atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than “naked” DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Atherosclerosis and Cardiovascular Diseases · Coronary Interventions and Diagnostics

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

Affiliations

Department of Physiology and Pathophysiology School of Basic Medical Sciences Hemorheology Center School of Basic Medical Sciences Peking University Beijing 100191 China

Key Laboratory of Molecular Cardiovascular Science Ministry of Education Beijing 100191 China

National Health Commission Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Peking University Beijing 100191 China

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

Department of Cardiovascular Surgery Peking University Shenzhen Hospital Shenzhen 518036 China

Center for Biomechanics and Bioengineering Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology Institute of Mechanics Chinese Academy of Sciences Beijing 100190 China

School of Engineering Sciences University of Chinese Academy of Sciences Beijing 100049 China

University of Chinese Academy of Sciences Beijing 100049 China

Funding

National Natural Science Foundation of China · Ministry of Science and Technology

References (52)

Show source-provided references
1. 10.1007/s11606-020-06070-z10.1007/s11606-020-06070-z ↗
2. 10.1152/physrev.00047.200910.1152/physrev.00047.2009 ↗
3. 10.1007/s10439-007-9426-310.1007/s10439-007-9426-3 ↗
4. 10.1161/CIRCULATIONAHA.120.05107810.1161/CIRCULATIONAHA.120.051078 ↗
5. 10.1016/j.tips.2019.02.00410.1016/j.tips.2019.02.004 ↗
6. 10.1016/j.jacc.2015.03.01610.1016/j.jacc.2015.03.016 ↗
7. 10.1002/adma.20211066010.1002/adma.202110660 ↗
8. 10.1021/acsnano.8b0887510.1021/acsnano.8b08875 ↗
9. 10.1021/acsami.8b1792810.1021/acsami.8b17928 ↗
10. 10.1161/CIRCRESAHA.119.31518510.1161/CIRCRESAHA.119.315185 ↗
11. 10.1021/acs.chemrev.6b0007310.1021/acs.chemrev.6b00073 ↗
12. 10.1002/wnan.136210.1002/wnan.1362 ↗
13. 10.1038/s41573-020-0090-810.1038/s41573-020-0090-8 ↗
14. 10.1088/0957-4484/20/49/49510110.1088/0957-4484/20/49/495101 ↗
15. 10.1166/jnn.2011.353610.1166/jnn.2011.3536 ↗
16. 10.1016/j.biomaterials.2006.05.02410.1016/j.biomaterials.2006.05.024 ↗
17. 10.1002/jcp.2898710.1002/jcp.28987 ↗
18. 10.1073/pnas.130500011010.1073/pnas.1305000110 ↗
19. 10.1016/j.jbiomech.2008.03.02110.1016/j.jbiomech.2008.03.021 ↗
20. 10.1038/nm.195510.1038/nm.1955 ↗
21. 10.1126/science.121781510.1126/science.1217815 ↗
22. 10.1038/s41598-017-15387-510.1038/s41598-017-15387-5 ↗
23. 10.1007/s12195-014-0325-z10.1007/s12195-014-0325-z ↗
24. 10.1172/JCI7479210.1172/JCI74792 ↗
25. 10.1016/j.ctrv.2017.01.00410.1016/j.ctrv.2017.01.004 ↗
26. 10.1186/s12967-020-02615-210.1186/s12967-020-02615-2 ↗
27. 10.1186/s13148-019-0709-y10.1186/s13148-019-0709-y ↗
28. 10.1039/C5NR08560H10.1039/C5NR08560H ↗
29. 10.1016/j.jconrel.2017.10.01210.1016/j.jconrel.2017.10.012 ↗
30. 10.1016/j.jconrel.2014.11.01110.1016/j.jconrel.2014.11.011 ↗
31. 10.1021/ja309812z10.1021/ja309812z ↗
32. 10.1039/C7NR04785A10.1039/C7NR04785A ↗
33. 10.1021/sc500152g10.1021/sc500152g ↗
34. 10.1016/S0021-9290(03)00210-010.1016/S0021-9290(03)00210-0 ↗
35. 10.1242/jcs.13831310.1242/jcs.138313 ↗
36. 10.1016/j.biopha.2016.09.07210.1016/j.biopha.2016.09.072 ↗
37. 10.1172/JCI9792410.1172/JCI97924 ↗
38. 10.1161/ATVBAHA.118.31156910.1161/ATVBAHA.118.311569 ↗
39. 10.3324/haematol.2020.24865810.3324/haematol.2020.248658 ↗
40. 10.1073/pnas.120990511010.1073/pnas.1209905110 ↗
41. 10.1021/nl403949h10.1021/nl403949h ↗
42. 10.1016/j.bbrc.2019.12.12910.1016/j.bbrc.2019.12.129 ↗
43. 10.1016/j.bioactmat.2021.10.03810.1016/j.bioactmat.2021.10.038 ↗
44. 10.1007/s10439-012-0634-010.1007/s10439-012-0634-0 ↗
45. 10.1177/153537021769311610.1177/1535370217693116 ↗
46. 10.1016/j.biomaterials.2013.04.01110.1016/j.biomaterials.2013.04.011 ↗
47. 10.1021/nn503732m10.1021/nn503732m ↗
48. 10.1016/j.jconrel.2019.07.02610.1016/j.jconrel.2019.07.026 ↗
49. 10.1038/s41467-018-06730-z10.1038/s41467-018-06730-z ↗
50. 10.1039/c0nr00893a10.1039/c0nr00893a ↗
51. Zhao C. R. · Proc. Natl. Acad. Sci. USA · 2021 · 118
52. 10.1152/ajpheart.00510.200910.1152/ajpheart.00510.2009 ↗