期刊
THERANOSTICS
卷 10, 期 15, 页码 6581-6598出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.45528
关键词
microvesicles; proinflammatory macrophages; CCL2/CCR2 signaling; SNARE-mediated membrane fusion; metastatic ovarian cancer
资金
- National Natural Science Foundation of China [81872805, 81603040]
- Guangdong Basic and Applied Basic Research Foundation [2016A030311008, 2017A030313819]
- Science and Technology Foundation of Guangzhou [201904010425]
- Fundamental Research Funds for the Central Universities [18ykpy24]
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery [2019B030301005]
Background: Exosome (Exo)-based chemotherapeutic drug delivery systems have been extensively investigated; however, the therapeutic potential of other subtypes of extracellular vesicles (EVs), in particular microvesicles (MiV), seem to be overlooked. Moreover, despite a general agreement on organ tropism of EVs, few studies have clearly demonstrated that EVs specifically target tumor tissue. Methods: Proinflammatory macrophage-derived EV subpopulations comprising apoptotic bodies (ApB), MiV and Exo were isolated under differential ultracentrifugation, and further analyzed using comparative proteomic and lipid approach. Results: On the basis of EV biogenesis pathways, our data demonstrated that MiV acquire the tumor-targeting capacity probably through inheritance of CCR2-enriched cell membrane which also drives the recruitment of donor cells to tumor sites. Further, our data validate MiV utilize SNARE-mediated membrane fusion to directly discharge doxorubicin to nucleus and bypass endocytic degradation. Conclusions: Compared with other EV subtypes, MiV loaded with doxorubicin gain significant benefits in chemotherapeutic outcomes including survival rate improvements in metastatic ovarian cancer. Therefore, MiV represent a potent alterative to Exo and synthetic liposomes (Lipo) for tumor-targeting drug delivery.
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