Enhancing GSDME-induced pyroptosis through low-dose doxorubicin/biflavonoid derivative co-loaded nanodisc in hepatocellular carcinoma.

ABSTRACT: The chemotherapeutic drug doxorubicin (DOX) has been demonstrated to trigger pyroptosis in tumor cells at exceptionally high concentrations. Nevertheless, the administration of DOX at suprapharmacological doses could cause acute off-target cytotoxicity and severe adverse effects. Herein, a biflavonoid derivative, F24, was found to improve the sensitivity of hepatocellular carcinoma (HCC) cells to low-dose DOX and reduce the adverse effects of DOX. We demonstrated that F24 synergized with low-dose DOX to increase pyroptosis and autophagy in HCC cells through dual-target CDK6 inhibition/p53 activation at a proper ratio. To achieve this synergistic effect, nanodiscs with large hydrophobic cavities were selected to codeliver the low-dose hydrophobic drugs DOX and F24 (DOX-F24@Nanodisc, DF@N),

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12646095 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature