An atom-edged magnetic nanomotor for cancer mechanotherapy

Mechanical force-induced lysosomal membrane permeabilization represents a promising cancer therapy by directly disrupting lysosomes to initiate programmed cell death. However, achieving precise and effective lysosomal disruption in vivo remains challenging. Here, we demonstrated that ultrathin (a thickness of ∼0.83 nm) magnetic graphene oxide (MagGO) nanomotors accumulate within the lysosomes of tumor cells. Under three-dimensional rotating fluctuating magnetic field (3D MF) control, MagGO generated robust mechanical pressure concentrated at its atomically sharp edges, effectively rupturing the lysosomal membrane and inducing cell death. Critically, the cytotoxic effect was tightly regulated by the frequency and mode of magnetic stimulation. Lysosomal disruption triggered cathepsin B leakage, activating multiple cell death pathways, predominantly pyroptosis. Importantly, MagGO treatment under 3D MF substantially suppressed tumor growth in three distinct tumor models (U87, A549, and MDA-MB-231), revealing strong therapeutic efficacy coupled with excellent biosafety. This work highlights a promising force-driven nanotherapeutic strategy for effective in vivo antitumor therapy.