Novel plasma-polymerized coating facilitates HeLa cell spheroid formation, exerting necroptosis via β-cyclodextrin-encapsulated resveratrol

Abstract

Beta-cyclodextrins (β-CDs) comprise a pore for accommodating resveratrol (Res), thereby boosting its bioavailability. Res-incorporated β -CD (Res/CD) may be cytotoxic against both normal and cancer cells. Herein, we examined whether Res/CD exhibits anticancer activity against tumor spheroids, similar to in vivo tumor mass. To prepare three-dimensional spheroids, 1,1,1,3,5,7,7,7 octamethyl-3,5-bis(trimethylsiloxyl) tetrasiloxane (OMBTSTS) was deposited to the surface of the culture dish via plasma polymerization. We observed that HeLa cells grew as spheroids on the OMBTSTS-deposited surface at 20 W plasma power. Res/CD was delivered to the hypoxic core of the spheroid, inducing necrosis, whereas Res was not. Consistently, 10 μM Res alone was not cytotoxic to two-dimensional HeLa cells grown on a culture dish and three-dimensional spheroids. However, Res/CD promoted the necroptosis of spheroids, which were split into small fragments, ultimately inducing cell spheroid death. Collectively, our data suggest that nontoxic levels of Res/CD were efficiently delivered to the hypoxic core of tumor spheroids, promoting cell death. Therefore, Res/CD can be used as an effective anticancer drug. Moreover, the plasma-polymerized OMBTSTS modification technique provides insights into the efficient formation of spheroids in various cancer cell lines.