An Intracellular Magnetic Micromotor Drives Spatiotemporal Mechano-Immunotherapy.

Abstract

Spatiotemporal coordination of coherent steps in the cancer-immunity cycle is desirable yet inherently challenging in nature, thereby impeding the effectiveness of immunotherapy in treating solid tumors. Here, this work designs an intelligent intracellular magnetic torque (IIMT) paradigm to spatiotemporally orchestrate tumor cells and antigen presenting cells (APCs) by integrating with rotating magnetic fields to drive immunotherapy. A rod-shaped magnetic micromotor is engineered to manipulate tunable torques inside lysosomes and regulate selective biological functions in these cells. High-intensity torques primarily cause tumor immunogenic cell death and antigen release, whereas, low intensity-torques trigger antigen leakage from lysosomes for APC cross-presentation and simultaneously activate NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Importantly, sequential IIMT boosts antitumor immunity and synergistically enhances anti-programmed cell death protein 1 antibody (anti-PD-1) therapeutic effect. In sum, this work develops a magnetic torque-based strategy to drive the cancer-immunity cycle for mechano-immunotherapy, which opens an intriguing field to explore mechanobiology and immunity through intracellular mechanics.