Microenvironment Mechanical Torque from ZnFe2O4 (ZFO) Micromotors Inhibiting Tumor Migration

Adv Mater. 2025 Jan 21:e2409769. doi: 10.1002/adma.202409769. Online ahead of print.

Abstract

Mechanical force attracts booming attention with the potential to tune the tumor cell behavior, especially in cell migration. However, the current approach for introducing mechanical input is difficult to apply in vivo. How the mechanical force affects cell behavior in situ also remains unclear. In this work, an intelligent miniaturized platform is constructed with magnetic ZnFe2O4 (ZFO) micromotors. The wireless ZFO can self-assemble in situ and rotate to generate mechanical torque of biologically relevant piconewton-scale at the target tumor site. It is observed unexpectedly that enhanced in situ mechanical rotating torque from ZFO micromotors and the active fluid inhibit the migration of highly invasive A549 tumor cells. The down-regulation of the Piezo1 channel and the suppressed signaling of ROCK1 in mechano-adaptive tumor cells is found to be related to the inhibition effect. With effectiveness confirmed with the zebrafish xenograft model, this platform provides a valuable toolkit for mechanobiology and force-associated non-invasive tumor therapy.

Keywords: ZnFe2O4 micromotor; mechanical torque; target tumor therapy; tumor microenvironment; tumor migration.