The authors present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively display cytotoxic ligand patterns in tumor microenvironments. The device is a pH-sensitive DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter under higher acidity (pH 6.5). This can effectively cluster death receptors (DRs) and trigger apoptosis of human breast cancer cells while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, the nanodevice decreased tumor growth by up to 70%. The study demonstrates the feasibility and potential of developing ligand pattern switches as a targeted treatment approach.The authors present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively display cytotoxic ligand patterns in tumor microenvironments. The device is a pH-sensitive DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter under higher acidity (pH 6.5). This can effectively cluster death receptors (DRs) and trigger apoptosis of human breast cancer cells while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, the nanodevice decreased tumor growth by up to 70%. The study demonstrates the feasibility and potential of developing ligand pattern switches as a targeted treatment approach.