Adhesion between EVs and tumor cells facilitated EV-encapsulated doxorubicin delivery via ICAM1
0301 basic medicine
Mice, Inbred BALB C
0303 health sciences
Antibiotics, Antineoplastic
Tumor Necrosis Factor-alpha
Mice, Nude
RM1-950
Extracellular vesicles
Intercellular Adhesion Molecule-1
ICAM1
Extracellular Vesicles
Mice
Drug Delivery Systems
Doxorubicin
TNF-α
Cell Line, Tumor
Neoplasms
Cell Adhesion
Animals
Humans
Female
Therapeutics. Pharmacology
IFN-γ
DOI:
10.1016/j.phrs.2024.107244
Publication Date:
2024-05-29T19:32:31Z
AUTHORS (13)
ABSTRACT
Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a "kiss-and-run" motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.
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CITATIONS (3)
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