Arresting the G2/M phase empowers synergy in magnetic nanomanipulator-based cancer mechanotherapy and chemotherapy.

Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors. The G2/M phase with the specific mechanical structure and redox environment was determined as the best sensitive stage to the intracellular magneto-mechanical regulation for cancer treatment. The G2/M phase could be a mechanical-targeted phase for synergistic therapy by combing the magneto-mechanical destruction with the cancer cell cycle-specific drugs. [Display omitted] • G2/M phase shows the best sensitivity to the intracellular magneto-mechanical regulation. • The mechanosensitivity of G2/M phase is related to cytoskeleton dynamics and redox environment. • G2/M phase is a mechanical-targeted phase for the synergistic mechano-chemical cancer therapy. [ABSTRACT FROM AUTHOR]