Milk-Derived Exosomes: Nanocarriers that Enhance Curcumin & Resveratrol Anticancer Activity

News release, Polyphenols Applications - 29 June 2022, Valencia - Spain

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. The objective of this study was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV).

A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined.

Milk-Derived Exosome Nanocarriers that Enhance Curcumin Resveratrol Anticancer Activity

Transmission electron microscopy observations of milk-derived EXOs isolated via the passive incubation method (scale bar: 200 nm).

The following results were obtained:

CUR and RSV peaked in the mammary tissue 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations.
Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed.
EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC).

Thus, milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. They enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells’ ABC-mediated chemoresistance.

Remember to secure a place at Polyphenols Applications 2022 conference to meet the brilliant researcher behind this study Dr. Juan Carlos Espín and benefit from his expertise. Register Early.

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