Targeting Decidual CD16 + Immune Cells with Exosome‐Based Glucocorticoid Nanoparticles for Miscarriage
Source abstract
Abstract
Abstract Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16 + NK cells and proinflammatory M1 macrophages at the maternal–fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue‐specific drug delivery systems, especially immune cell‐specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC‐Exo‐CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC‐Exo‐CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16 + decidual natural killer (NK) cells and CD16 + macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion‐prone mice. The developed GC‐Exo‐CD16Ab provides a feasible platform for precise and tissue‐specific therapeutic strategies for miscarriage and pregnancy‐related diseases.
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Research context
OpenAlex topics: Reproductive System and Pregnancy · Pregnancy and preeclampsia studies · Extracellular vesicles in disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Reproductive Medicine Center Department of Obstetrics and Gynecology Renmin Hospital of Wuhan University Wuhan University Wuhan 430072 China
TaiKang Medical School (School of Basic Medical Sciences) Renmin Hospital of Wuhan University Wuhan University Wuhan 430072 China
Shenzhen Key Laboratory of Reproductive Immunology for Peri‐implantation Guangdong Engineering Technology Research Center of Reproductive Immunology for Peri‐implantation Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital) Shenzhen 518000 China
Xinjiang Key Laboratory of Oncology Fifth Department of Gynecologic Surgery Xinjiang Medical University Affiliated Tumor Hospital Urumqi 830000 China
South China Institute of Environmental Sciences Ministry of Ecology and Environment Guangzhou 510655 China
Hubei Key Laboratory of Biomass Resource Chemistry and Environmental Biotechnology School of Resource and Environmental Science Wuhan University Wuhan 430079 China
Funding
National Natural Science Foundation of China · Fundamental Research Funds for the Central Universities · Basic and Applied Basic Research Foundation of Guangdong Province
References (82)
Show source-provided references
1. 10.1016/S0140-6736(21)00682-610.1016/S0140-6736(21)00682-6 ↗
2. 10.1155/2022/756770810.1155/2022/7567708 ↗
3. 10.1016/j.immuni.2017.11.01810.1016/j.immuni.2017.11.018 ↗
4. 10.1038/s41385-020-00374-310.1038/s41385-020-00374-3 ↗
5. 10.1016/j.gpb.2020.11.00210.1016/j.gpb.2020.11.002 ↗
6. 10.4049/jimmunol.220043310.4049/jimmunol.2200433 ↗
7. 10.3390/biology1203040210.3390/biology12030402 ↗
8. 10.7150/thno.7846710.7150/thno.78467 ↗
9. 10.7150/ijbs.4614410.7150/ijbs.46144 ↗
10. 10.1016/j.gim.2022.04.00510.1016/j.gim.2022.04.005 ↗
11. 10.1038/srep3431010.1038/srep34310 ↗
12. 10.1073/pnas.141732011210.1073/pnas.1417320112 ↗
13. 10.3389/fimmu.2021.66366010.3389/fimmu.2021.663660 ↗
14. 10.1126/sciimmunol.abb780010.1126/sciimmunol.abb7800 ↗
15. 10.3389/fimmu.2021.72829110.3389/fimmu.2021.728291 ↗
16. 10.1620/tjem.193.1310.1620/tjem.193.13 ↗
17. 10.1016/j.jri.2020.10326410.1016/j.jri.2020.103264 ↗
18. 10.1111/jcpt.1362910.1111/jcpt.13629 ↗
19. 10.1093/cid/ciad47410.1093/cid/ciad474 ↗
20. 10.2147/DMSO.S24737910.2147/DMSO.S247379 ↗
21. 10.1007/s11914-019-00498-x10.1007/s11914-019-00498-x ↗
22. 10.1136/ard.2008.09216310.1136/ard.2008.092163 ↗
23. 10.1093/humrep/dew18610.1093/humrep/dew186 ↗
24. 10.1007/s13346-024-01515-y10.1007/s13346-024-01515-y ↗
25. 10.3390/biomedicines908106110.3390/biomedicines9081061 ↗
26. 10.1016/j.tcb.2023.06.00610.1016/j.tcb.2023.06.006 ↗
27. 10.1186/s12951-024-02298-710.1186/s12951-024-02298-7 ↗
28. 10.1016/j.bioactmat.2023.08.00610.1016/j.bioactmat.2023.08.006 ↗
29. 10.1093/neuonc/noad19910.1093/neuonc/noad199 ↗
30. 10.1126/sciadv.abp943510.1126/sciadv.abp9435 ↗
31. 10.1021/acs.molpharmaceut.2c0053310.1021/acs.molpharmaceut.2c00533 ↗
32. 10.1111/jcmm.1623410.1111/jcmm.16234 ↗
33. 10.1186/s13287-020-01720-910.1186/s13287-020-01720-9 ↗
34. 10.1093/humrep/dey03710.1093/humrep/dey037 ↗
35. 10.7150/ijbs.6781610.7150/ijbs.67816 ↗
36. 10.1186/s12935-021-02089-210.1186/s12935-021-02089-2 ↗
37. 10.3390/ijms23191131210.3390/ijms231911312 ↗
38. 10.1016/j.jgg.2023.04.01210.1016/j.jgg.2023.04.012 ↗
39. 10.1096/fj.202201505RRRR10.1096/fj.202201505RRRR ↗
40. 10.3390/ijms2113463510.3390/ijms21134635 ↗
41. 10.3390/cells1114212610.3390/cells11142126 ↗
42. 10.2147/ITT.S30610910.2147/ITT.S306109 ↗
43. 10.3390/ijms24231688210.3390/ijms242316882 ↗
44. 10.1016/j.placenta.2023.04.00410.1016/j.placenta.2023.04.004 ↗
45. 10.1073/pnas.212066711910.1073/pnas.2120667119 ↗
46. 10.1038/s41467-023-36740-510.1038/s41467-023-36740-5 ↗
47. Wu X. · Clin. Dev. Immunol. · 2012 · 2012
48. 10.1016/j.it.2011.06.01310.1016/j.it.2011.06.013 ↗
49. 10.1111/imr.1308010.1111/imr.13080 ↗
50. 10.1038/nri.2017.6410.1038/nri.2017.64 ↗
51. 10.3389/fimmu.2019.0231710.3389/fimmu.2019.02317 ↗
52. 10.3389/fimmu.2020.52204710.3389/fimmu.2020.522047 ↗
53. 10.1038/s41581-022-00670-010.1038/s41581-022-00670-0 ↗
54. 10.1016/j.phymed.2023.15497410.1016/j.phymed.2023.154974 ↗
55. 10.1016/j.freeradbiomed.2022.08.03710.1016/j.freeradbiomed.2022.08.037 ↗
56. 10.3390/ijms23241594210.3390/ijms232415942 ↗
57. 10.3389/fphys.2023.113170110.3389/fphys.2023.1131701 ↗
58. 10.3389/fimmu.2021.64239210.3389/fimmu.2021.642392 ↗
59. 10.1038/s41423-019-0204-610.1038/s41423-019-0204-6 ↗
60. 10.3389/fimmu.2021.71483210.3389/fimmu.2021.714832 ↗
61. 10.1089/scd.2018.001510.1089/scd.2018.0015 ↗
62. 10.1186/s12943-021-01492-710.1186/s12943-021-01492-7 ↗
63. 10.18632/aging.10146510.18632/aging.101465 ↗
64. 10.2147/JIR.S30780110.2147/JIR.S307801 ↗
65. Bosch T. P. · Front. Immunol. · 2017 · 8 · 346
66. 10.1016/j.joca.2021.04.00610.1016/j.joca.2021.04.006 ↗
67. 10.1016/j.intimp.2023.11039210.1016/j.intimp.2023.110392 ↗
68. 10.1126/sciadv.abd386510.1126/sciadv.abd3865 ↗
69. 10.1186/s13287-020-01881-710.1186/s13287-020-01881-7 ↗
70. 10.1186/s13287-024-03652-010.1186/s13287-024-03652-0 ↗
71. 10.1186/s12943-022-01569-x10.1186/s12943-022-01569-x ↗
72. 10.1016/j.semcancer.2022.09.00410.1016/j.semcancer.2022.09.004 ↗
73. 10.1016/j.fertnstert.2020.10.03110.1016/j.fertnstert.2020.10.031 ↗
74. 10.1093/eurheartj/ehab92010.1093/eurheartj/ehab920 ↗
75. 10.1038/s41467-017-00269-110.1038/s41467-017-00269-1 ↗
76. 10.1016/j.intimp.2023.11084010.1016/j.intimp.2023.110840 ↗
77. 10.1056/NEJMra05054110.1056/NEJMra050541 ↗
78. 10.1186/s13058-017-0823-810.1186/s13058-017-0823-8 ↗
79. 10.1186/s13287-022-03010-y10.1186/s13287-022-03010-y ↗
80. 10.7150/thno.7356810.7150/thno.73568 ↗
81. 10.1093/humupd/dmaa04910.1093/humupd/dmaa049 ↗
82. 10.1016/j.jconrel.2022.12.02710.1016/j.jconrel.2022.12.027 ↗