Functional nanoplatform for modulating cellular forces to enhance antitumor immunity via mechanotransduction

Immune cells are sensitive to the perception of mechanical stimuli in the tumor microenvironment. Changes in biophysical cues within tumor tissue can alter the force-sensing mechanisms experienced by cells. Mechanical stimuli within the extracellular matrix are transformed into biochemical signals through mechanotransduction. Delving into how these minute biophysical cues affect the activation of immune cells, metabolic reprogramming, and subsequent effector functions could offer perspectives on therapeutic interventions for immune-related disorders. Our study used a ternary phycocyanin-podophyllotoxin-IDO1 self-assembled nanoplatform to investigate molecule-scale regulation of mechanical cues in the tumor microenvironment on immune cell functions to modulate immune responses. After treatment, a caspase cascade was mediated by remodeling mechanical cues, including cytoskeleton-related assembly, force channel activation, and metabolic reprogramming, all of which contributed to enhancing anti-tumor immunity via mechanotransduction. The results will be helpful for understanding the interaction between cell force remodeling and antitumor immunity via mechanotransduction.