Targeting and disrupting cytoskeleton using core-shell metal-organic framework nanoparticles to inhibit cancer cell migration

Cancer metastasis is driven by the motility of cancer cells, a process governed by the actin cytoskeleton. However, current actin-disrupting drugs aimed at inhibiting cancer cell migration suffer from poor selectivity and off-target effects. In this study, we present core-shell metal-organic framework nanoparticles designed to specifically target and disrupt the actin cytoskeleton in migratory cancer cells. We demonstrate that the migration and invasion of breast and prostate cancer cells can be significantly inhibited by targeting a migration-associated surface marker, epithelial cell adhesion molecule (EpCAM), using low-dose EpCAM antibody functionalized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs@Ab). Single-cell imaging reveals that the observed inhibition of cell migration results from disruption of the actin cytoskeleton. Mechanistic investigations highlight the synergistic roles of the degradable ZIF-8 nanoparticle core and the EpCAM-targeted antibody shell in cytoskeletal disruption. Given the widespread expression of cancer cell migration-related surface markers and the universal actin-disrupting activity of ZIF-8 NPs, this nanoparticle system provides a versatile, effective, and potentially safer strategy to inhibit cancer cell motility.