The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, DRs are also ubiquitously expressed in healthy tissue. Here we present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively turn on the display of cytotoxic ligand patterns in tumour microenvironments. We demonstrate a switchable DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter once under higher acidity. This can effectively cluster DRs and trigger apoptosis of human breast cancer cells at pH 6.5 while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, this nanodevice decreased tumour growth by up to 70%. The data demonstrate the feasibility and opportunities for developing ligand pattern switches as a path for targeted treatment.

膜上死亡受体 (DR) 的聚集会导致细胞凋亡。为了治疗肿瘤，启动这一机制的多价分子工具已经被开发出来。然而，DR 在健康组织中也普遍表达。在这里，我们提出了一种刺激响应机器人开关纳米装置，它可以自主地、选择性地打开肿瘤微环境中细胞毒性配体模式的显示。我们展示了一种可切换的 DNA 折纸，通常隐藏六个配体，但一旦在较高的酸度下，它们就会显示为直径 10 nm 的六边形图案。这可以有效地聚集 DR，并在 pH 6.5 下触发人乳腺癌细胞凋亡，同时在 pH 7.4 下保持惰性。当给携带人类乳腺癌异种移植物的小鼠施用这种纳米装置时，肿瘤生长减少了高达 70%。这些数据证明了开发配体模式开关作为靶向治疗途径的可行性和机会。