An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

Nature creates specific structures to control mechanical plasticity for cell fate regulation. Although immune cells can sense and adapt to extracellular mechanical cues, how to activate immune responses via intracellular mechanical stimulation remains a mystery. Here, we present an intelligent intracellular magnetic torque (IIMT) paradigm that is coupled with programmed rotating magnetic fields to generate the selective mechano-stimulations in lysosomes and induce sequential antitumor immune responses. A magnetic rod-shaped micromotor (MagRM) with the a unique geometric aspect ratio is designed to exert tunable torques in antigen-presenting cells (APCs) and tumor cells. Low-intensity torque induces the mild lysosomal membrane damage to trigger antigen cross-presentation and canonical NLRP3 inflammasome activation in APCs, whereas high-intensity torque causes lysosomal membrane rupture for immunogenic cell death. In vivo studies unveil that the optimal antitumor activity is achieved by generating sequential torques from high to low intensities, which is illuminating to explore mechano-immunotherapy with selective and spatiotemporal control. Overall design: The underlying mechanism of mechano-regulation for tumor cell death post high-frequency megneic field (HMF) were explored for the analysis. The RNA sequencing was performed on OVA-expression B16F10 (B16-OVA) melanoma cells collected at 6 h after Control, magnetic rod-shaped micromotors (MagRMs) with HMF treatments.