journal article·2024-04-10Open access

Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules

Kenta Morimoto, Jojiro Ishitobi, Kosuke Noguchi, Ryoichi Kira, Yukiya Kitayama, Yuto Goto, Daisuke Fujiwara, Masataka Michigami, Atsushi Harada, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki, Masamitsu Kanada, Ikuhiko Nakase

ACS Applied Materials & Interfaces· Volume 16· Issue 14

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), transfer bioactive molecules from donor to recipient cells in various pathophysiological settings, thereby mediating intercellular communication. Despite their significant roles in extracellular signaling, the cellular uptake mechanisms of different EV subpopulations remain unknown. In particular, plasma membrane-derived MVs are larger vesicles (100 nm to 1 μm in diameter) and may serve as efficient molecular delivery systems due to their large capacity; however, because of size limitations, receptor-mediated endocytosis is considered an inefficient means for cellular MV uptake. This study demonstrated that macropinocytosis (lamellipodia formation and plasma membrane ruffling, causing the engulfment of large fluid volumes outside cells) can enhance cellular MV uptake. We developed experimental techniques to induce macropinocytosis-mediated MV uptake by modifying MV membranes with arginine-rich cell-penetrating peptides for the intracellular delivery of therapeutic molecules.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · RNA Interference and Gene Delivery · MicroRNA in disease regulation

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

Affiliations

Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan

Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Osaka, Japan

Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, 11-68, Koshien Kyuban-cho, Nishinomiya 663-8179, Hyogo, Japan

Institute for Bioscience, Mukogawa Women’s University, 11-68, Koshien Kyuban-cho, Nishinomiya 663-8179, Hyogo, Japan

Institute for Chemical Research, Kyoto University

Institute for Quantitative Health Science and Engineering (IQ), Michigan State University

Department of Pharmacology and Toxicology

College of Human Medicine, Michigan State University

Funding

Naito Foundation · Takeda Science Foundation · Core Research for Evolutional Science and Technology · Institute for Chemical Research, Kyoto University · Osaka Metropolitan University

References (57)

Show source-provided references
1. 10.1002/pros.2285310.1002/pros.22853 ↗
2. 10.1038/ncb159610.1038/ncb1596 ↗
3. 10.1016/j.cub.2018.01.05910.1016/j.cub.2018.01.059 ↗
4. 10.1016/j.dmpk.2021.10043510.1016/j.dmpk.2021.100435 ↗
5. 10.1007/s11095-022-03463-z10.1007/s11095-022-03463-z ↗
6. 10.3390/ijms2402157110.3390/ijms24021571 ↗
7. 10.1038/srep1030010.1038/srep10300 ↗
8. 10.3390/pr902022410.3390/pr9020224 ↗
9. 10.1016/S0962-8924(00)89101-110.1016/S0962-8924(00)89101-1 ↗
10. 10.1083/jcb.20011206710.1083/jcb.200112067 ↗
11. 10.1038/nrm244710.1038/nrm2447 ↗
12. 10.1038/nature0145110.1038/nature01451 ↗
13. 10.3389/fendo.2017.0026110.3389/fendo.2017.00261 ↗
14. 10.3390/cancers1420505610.3390/cancers14205056 ↗
15. 10.1038/nature1213810.1038/nature12138 ↗
16. 10.1016/j.chembiol.2012.09.01110.1016/j.chembiol.2012.09.011 ↗
17. 10.1158/1541-7786.MCR-18-089110.1158/1541-7786.MCR-18-0891 ↗
18. 10.1016/j.ymthe.2004.08.01010.1016/j.ymthe.2004.08.010 ↗
19. 10.1021/bi061282410.1021/bi0612824 ↗
20. 10.1021/acs.accounts.7b0022110.1021/acs.accounts.7b00221 ↗
21. 10.1038/srep3493710.1038/srep34937 ↗
22. 10.1039/C6CC06719K10.1039/C6CC06719K ↗
23. 10.1038/s41598-017-02014-610.1038/s41598-017-02014-6 ↗
24. 10.1002/2211-5463.1310710.1002/2211-5463.13107 ↗
25. 10.1021/acs.molpharmaceut.1c0024410.1021/acs.molpharmaceut.1c00244 ↗
26. 10.1021/acs.molpharmaceut.1c0088210.1021/acs.molpharmaceut.1c00882 ↗
27. 10.1016/j.bbrc.2014.03.01810.1016/j.bbrc.2014.03.018 ↗
28. 10.1074/jbc.M117.79241610.1074/jbc.M117.792416 ↗
29. 10.1038/ncb172510.1038/ncb1725 ↗
30. 10.1182/blood-2011-01-33087810.1182/blood-2011-01-330878 ↗
31. 10.1002/ggn2.20210005510.1002/ggn2.202100055 ↗
32. 10.3389/fonc.2022.87052810.3389/fonc.2022.870528 ↗
33. 10.1002/art.4192010.1002/art.41920 ↗
34. 10.1016/j.ceb.2020.06.00510.1016/j.ceb.2020.06.005 ↗
35. 10.3389/fcell.2020.0020110.3389/fcell.2020.00201 ↗
36. 10.3390/biomedicines1006135710.3390/biomedicines10061357 ↗
37. 10.1083/jcb.107.2.80110.1083/jcb.107.2.801 ↗
38. 10.1242/jcs.0323810.1242/jcs.03238 ↗
39. 10.1038/mt.2009.19210.1038/mt.2009.192 ↗
40. 10.1042/BC2006012310.1042/BC20060123 ↗
41. 10.1002/jgm.55310.1002/jgm.553 ↗
42. 10.1038/s41598-017-03036-w10.1038/s41598-017-03036-w ↗
43. 10.1016/S0898-6568(01)00190-510.1016/S0898-6568(01)00190-5 ↗
44. 10.1038/nrm125710.1038/nrm1257 ↗
45. 10.1016/j.ceb.2009.05.00210.1016/j.ceb.2009.05.002 ↗
46. 10.1074/jbc.272.18.1180510.1074/jbc.272.18.11805 ↗
47. 10.1161/01.RES.0000159708.71142.c810.1161/01.RES.0000159708.71142.c8 ↗
48. 10.1111/j.1600-0838.2009.00941.x10.1111/j.1600-0838.2009.00941.x ↗
49. 10.1161/01.RES.0000225283.71490.5a10.1161/01.RES.0000225283.71490.5a ↗
50. 10.3390/ijms2005103310.3390/ijms20051033 ↗
51. 10.3390/molecules2416293010.3390/molecules24162930 ↗
52. 10.1186/1471-2210-11-410.1186/1471-2210-11-4 ↗
53. 10.1111/cas.1374110.1111/cas.13741 ↗
54. 10.1021/acsami.6b1463310.1021/acsami.6b14633 ↗
55. 10.7150/thno.3352010.7150/thno.33520 ↗
56. 10.1007/s12195-022-00738-810.1007/s12195-022-00738-8 ↗
57. 10.1038/nature2234110.1038/nature22341 ↗