Dynamic magneto-mechanical force in lysosomes instructs durable macrophage repolarization for antitumor immunity.
Mechanical forces are the emerging physical cue to regulate biochemical signals of immune cells for antitumor immunity. Here, we develop a magneto-mechanical force-triggered lysosomal membrane permeabilization (MagLMP) strategy to dictate durable macrophage repolarization, which leads to dynamic damage of lysosomal membrane via the finely tuned torque-induced vortex. We found that the MagLMP could activate M1-like macrophage repolarization, followed by the mounting of antitumor immunity. Together, we establish an intracellular mechanical strategy to dynamically manipulate innate immune responses in vivo and provide the tool for durable immunotherapy through organelle mechanotransduction. Overall design: The experiment is aim to investigate the repolarization of macrophages after stimulated by magneto-mechanical force in lysosomes.  Magnetic nanomotors were cocultured with RAW 264.7 macrophages, and then cells were stimulated by rotation magnetic field at the frequency of 1 Hz.