Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models.
Cannabidiol
Doxorubicin and triple negative breast cancer
Extracellular vesicles
Sensitization
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
25 Sep 2021
25 Sep 2021
Historique:
received:
03
05
2021
revised:
19
07
2021
accepted:
22
07
2021
pubmed:
30
7
2021
medline:
23
9
2021
entrez:
29
7
2021
Statut:
ppublish
Résumé
Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1 ± 1.02 nm, zeta potential of -30.26 ± 0.12 mV, entrapment efficiency of 92.3 ± 2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74 ± 2.44% and 53.99 ± 1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Our in-vitro studies demonstrated that CBD either alone or in EVs form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P < 0.05). Flow cytometry and migration studies revealed that CBD EVs either alone or in combination with DOX induced G1 phase cell cycle arrest and decreased migration of MDA-MB-231 cells, respectively. CBD EVs and DOX combination significantly reduced tumor burden (***P < 0.001) in MDA-MB-231 xenograft tumor model. Western blotting and immunocytochemical analysis demonstrated that CBD EVs and DOX combination decreased the expression of proteins involved in inflammation, metastasis and increased the expression of proteins involved in apoptosis. CBD EVs and DOX combination will have profound clinical significance in not only decreasing the side effects but also increasing the therapeutic efficacy of DOX in TNBC.
Identifiants
pubmed: 34324983
pii: S0378-5173(21)00749-3
doi: 10.1016/j.ijpharm.2021.120943
pmc: PMC8528640
mid: NIHMS1739672
pii:
doi:
Substances chimiques
Cannabidiol
19GBJ60SN5
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
120943Subventions
Organisme : NIMHD NIH HHS
ID : U54 MD007582
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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